Pyrrolopyridine inhibitors of kinases

ABSTRACT

The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, 
     
       
         
         
             
             
         
       
     
     wherein R 1a , R 1b , R 1c , X, and Y are defined in the description. The present invention relates also to compositions containing said compounds which are useful for inhibiting kinases such as Cdc7 and methods of treating diseases such as cancer.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application Ser.No. 61/325,591 filed Apr. 19, 2010, which is incorporated by referencein its entirety.

BACKGROUND OF THE INVENTION

Eukaryotic cells divide by a directed, step-wise process referred to asthe cell cycle. Cells must first replicate their DNA in S phase beforeseparating their sister chromatids in mitosis (karyokinesis) andsplitting off into two daughter cells (cytokinesis). In mammalian cells,DNA replication must be initiated at multiple sites (replicationorigins) throughout the genome to ensure that all the genetic materialis duplicated prior to mitosis. To maintain genome integrity, DNA mustbe replicated only once per cell cycle, and so this process is highlyregulated and governed by checkpoints. Before replication is initiated,origins must be licensed through the formation of pre-replicationcomplexes (pre-RCs) in early G1. Formation of pre-RCs involves thestep-wise binding of the origin recognition complex (ORC) to originsfollowed by the binding of the loading factors Cdc6 and Cdt1. Theseproteins then recruit the putative DNA replicative helicase complex,MCM2-7. Once this pre-RC is formed, replication initiation requires theactivation of S-phase-promoting serine/threonine kinases, Cyclin/Cdksand Cdc7/Dbf4. These kinases consist of an enzymatic subunit (CDKs andCdc7) and a regulatory sub-unit (Cyclins for CDKs; Dbf4 or Drf1 forCdc7). They phosphorylate multiple MCMs in pre-RCs in a sequentialmanner, thereby activating the helicase and recruiting other DNAreplication factors (Cdc45, GINS complex, etc.) for DNA synthesis (forreviews, see Kim et al., 2003; Kim et al., 2004; Lau et al., 2006; Lauet al., 2007; Stillman, 2005). MCM2 Serine-40 and Serine-53 arewell-characterized phosphorylation sites for Cdc7/Dbf4 (Cho et al.,2006; Montagnoli et al., 2006; Tsuji et al., 2006).

Inhibiting regulators of replication initiation, such as Cdc6, Cdc7/Dbf4or Cdc7/Drf1, has lethal consequences in cancerous cells, whereas normalcells are able to arrest and resume normal divisions once initiationactivity is restored (Feng et al., 2003; Montagnoli et al., 2004; seeLau and Jiang, 2006, for review). Small molecule inhibitors of theprotein kinase Cdc7 are thus attractive candidates for therapeuticintervention in cancer, inflammation and other cell proliferativedisorders.

SUMMARY OF THE INVENTION

The present invention has numerous embodiments. One embodiment of thisinvention, therefore, pertains to compounds that have formula (I)

wherein R^(1a), R^(1b), R^(1c), X, and Y are as defined below andsubsets therein.

Also provided are pharmaceutically acceptable compositions, comprising atherapeutically effective amount of a compound of formula (I) apharmaceutically acceptable salt in combination with a pharmaceuticallysuitable carrier.

One embodiment is directed to a method of treating cancer in a mammalcomprising administering thereto a therapeutically acceptable amount ofa compound or pharmaceutically acceptable salt of formula (I). In yetanother embodiment pertains to a method of decreasing tumor volume in amammal comprising administering thereto a therapeutically acceptableamount of a compound or pharmaceutically acceptable salt of formula (I).

DETAILED DESCRIPTION OF THE INVENTION

This detailed description is intended only to acquaint others skilled inthe art with Applicants' invention, its principles, and its practicalapplication so that others skilled in the art may adapt and apply theinvention in its numerous forms, as they may be best suited to therequirements of a particular use. This description and its specificexamples are intended for purposes of illustration only. This invention,therefore, is not limited to the embodiments described in this patentapplication, and may be variously modified.

Abbreviations and Definitions

Unless otherwise defined herein, scientific and technical terms used inconnection with the present invention shall have the meanings that arecommonly understood by those of ordinary skill in the art. The meaningand scope of the terms should be clear, however, in the event of anylatent ambiguity, definitions provided herein take precedent over anydictionary or extrinsic definition. In this application, the use of “or”means “and/or” unless stated otherwise. Furthermore, the use of the term“including”, as well as other forms, such as “includes” and “included”,is not limiting. With reference to the use of the words “comprise” or“comprises” or “comprising” in this patent application (including theclaims), Applicants note that unless the context requires otherwise,those words are used on the basis and clear understanding that they areto be interpreted inclusively, rather than exclusively, and thatApplicants intend each of those words to be so interpreted in construingthis patent application, including the claims below. For a variable thatoccurs more than one time in any substituent or in the compound of theinvention or any other formulae herein, its definition on eachoccurrence is independent of its definition at every other occurrence.Combinations of substituents are permissible only if such combinationsresult in stable compounds. Stable compounds are compounds which can beisolated in a useful degree of purity from a reaction mixture.

It is meant to be understood that proper valences are maintained for allcombinations herein, that monovalent moieties having more than one atomare attached through their left ends, and that divalent moieties aredrawn from left to right.

As used in the specification and the appended claims, unless specifiedto the contrary, the following terms have the meaning indicated:

The term “alkyl” (alone or in combination with another term(s)) means astraight- or branched-chain saturated hydrocarbyl substituent typicallycontaining from 1 to about 10 carbon atoms; or in another embodiment,from 1 to about 8 carbon atoms; in another embodiment, from 1 to about 6carbon atoms; and in another embodiment, from 1 to about 4 carbon atoms.Examples of such substituents include methyl, ethyl, n-propyl,isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, iso-amyl,and hexyl and the like.

The term “alkenyl” (alone or in combination with another term(s)) meansa straight- or branched-chain hydrocarbyl substituent containing one ormore double bonds and typically from 2 to about 10 carbon atoms; or inanother embodiment, from 2 to about 8 carbon atoms; in anotherembodiment, from 2 to about 6 carbon atoms; and in another embodiment,from 2 to about 4 carbon atoms. Examples of such substituents includeethenyl(vinyl), 2-propenyl, 3-propenyl, 1,4-pentadienyl, 1,4-butadienyl,1-butenyl, 2-butenyl, and 3-butenyl and the like.

The term “alkynyl” (alone or in combination with another term(s)) meansa straight- or branched-chain hydrocarbyl substituent containing one ormore triple bonds and typically from 2 to about 10 carbon atoms; or inanother embodiment, from 2 to about 8 carbon atoms; in anotherembodiment, from 2 to about 6 carbon atoms; and in another embodiment,from 2 to about 4 carbon atoms. Examples of such substituents includeethynyl, 2-propynyl, 3-propynyl, 2-butynyl, and 3-butynyl and the like.

The term “carbocyclyl” (alone or in combination with another term(s))means a saturated cyclic (i.e., “cycloalkyl”), partially saturatedcyclic (i.e., “cycloalkenyl”), or completely unsaturated (i.e., “aryl”)hydrocarbyl substituent containing from 3 to 14 carbon ring atoms (“ringatoms” are the atoms bound together to form the ring or rings of acyclic substituent). A carbocyclyl may be a single-ring (monocyclic) orpolycyclic ring structure.

A carbocyclyl may be a single ring structure, which typically containsfrom 3 to 8 ring atoms, more typically from 3 to 6 ring atoms, and evenmore typically 5 to 6 ring atoms. Examples of such single-ringcarbocyclyls include cyclopropyl (cyclopropanyl), cyclobutyl(cyclobutanyl), cyclopentyl (cyclopentanyl), cyclopentenyl,cyclopentadienyl, cyclohexyl (cyclohexanyl), cyclohexenyl,cyclohexadienyl, and phenyl. A carbocyclyl may alternatively bepolycyclic (i.e., may contain more than one ring). Examples ofpolycyclic carbocyclyls include bridged, fused, and spirocycliccarbocyclyls. In a spirocyclic carbocyclyl, one atom is common to twodifferent rings. An example of a spirocyclic carbocyclyl isspiropentanyl. In a bridged carbocyclyl, the rings share at least twocommon non-adjacent atoms. Examples of bridged carbocyclyls includebicyclo[2.2.1]heptanyl, bicyclo[2.2.1]hept-2-enyl, and adamantanyl. In afused-ring carbocyclyl system, two or more rings may be fused together,such that two rings share one common bond. Examples of two- orthree-fused ring carbocyclyls include naphthalenyl,tetrahydronaphthalenyl (tetralinyl), indenyl, indanyl (dihydroindenyl),anthracenyl, phenanthrenyl, and decalinyl.

The term “cycloalkyl” (alone or in combination with another term(s))means a saturated cyclic hydrocarbyl substituent containing from 3 to 14carbon ring atoms. A cycloalkyl may be a single carbon ring, whichtypically contains from 3 to 8 carbon ring atoms and more typically from3 to 6 ring atoms. Examples of single-ring cycloalkyls includecyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. A cycloalkyl mayalternatively be polycyclic or contain more than one ring. Examples ofpolycyclic cycloalkyls include bridged, fused, and spirocycliccarbocyclyls.

The term “aryl” (alone or in combination with another term(s)) means anaromatic carbocyclyl containing from 6 to 14 carbon ring atoms. Examplesof aryls include phenyl, naphthalenyl, and indenyl.

In some instances, the number of carbon atoms in a hydrocarbylsubstituent (e.g., alkyl, alkenyl, alkynyl, or cycloalkyl) is indicatedby the prefix “C_(x)-C_(y)-”, wherein x is the minimum and y is themaximum number of carbon atoms in the substituent. Thus, for example,“C₁-C₆-alkyl” refers to an alkyl substituent containing from 1 to 6carbon atoms. Illustrating further, C₃-C₈-cycloalkyl means a saturatedhydrocarbyl ring containing from 3 to 8 carbon ring atoms.

The term “hydrogen” (alone or in combination with another term(s)) meansa hydrogen radical, and may be depicted as —H.

The term “hydroxy” (alone or in combination with another term(s)) means—OH.

The term “carboxy” (alone or in combination with another term(s)) means—C(O)—OH.

The term “amino” (alone or in combination with another term(s)) means—NH₂.

The term “halogen” or “halo” (alone or in combination with anotherterm(s)) means a fluorine radical (which may be depicted as —F),chlorine radical (which may be depicted as —Cl), bromine radical (whichmay be depicted as —Br), or iodine radical (which may be depicted as—I).

If a substituent is described as being “substituted”, a non-hydrogenradical is in the place of hydrogen radical on a carbon or nitrogen ofthe substituent. Thus, for example, a substituted alkyl substituent isan alkyl substituent in which at least one non-hydrogen radical is inthe place of a hydrogen radical on the alkyl substituent. To illustrate,monofluoroalkyl is alkyl substituted with a fluoro radical, anddifluoroalkyl is alkyl substituted with two fluoro radicals. It shouldbe recognized that if there are more than one substitution on asubstituent, each non-hydrogen radical may be identical or different(unless otherwise stated).

If a substituent is described as being “optionally substituted”, thesubstituent may be either (1) not substituted or (2) substituted. If asubstituent is described as being optionally substituted with up to aparticular number of non-hydrogen radicals, that substituent may beeither (1) not substituted; or (2) substituted by up to that particularnumber of non-hydrogen radicals or by up to the maximum number ofsubstitutable positions on the substituent, whichever is less. Thus, forexample, if a substituent is described as a heteroaryl optionallysubstituted with up to 3 non-hydrogen radicals, then any heteroaryl withless than 3 substitutable positions would be optionally substituted byup to only as many non-hydrogen radicals as the heteroaryl hassubstitutable positions. To illustrate, tetrazolyl (which has only onesubstitutable position) would be optionally substituted with up to onenon-hydrogen radical. To illustrate further, if an amino nitrogen isdescribed as being optionally substituted with up to 2 non-hydrogenradicals, then a primary amino nitrogen will be optionally substitutedwith up to 2 non-hydrogen radicals, whereas a secondary amino nitrogenwill be optionally substituted with up to only 1 non-hydrogen radical.

This patent application uses the terms “substituent” and “radical”interchangeably.

The prefix “halo” indicates that the substituent to which the prefix isattached is substituted with one or more independently selected halogenradicals. For example, haloalkyl means an alkyl substituent in which atleast one hydrogen radical is replaced with a halogen radical. Examplesof haloalkyls include chloromethyl, 1-bromoethyl, fluoromethyl,difluoromethyl, trifluoromethyl, and 1,1,1-trifluoroethyl. It should berecognized that if a substituent is substituted by more than one halogenradical, those halogen radicals may be identical or different (unlessotherwise stated).

The prefix “perhalo” indicates that every hydrogen radical on thesubstituent to which the prefix is attached is replaced withindependently selected halogen radicals, i.e., each hydrogen radical onthe substituent is replaced with a halogen radical. If all the halogenradicals are identical, the prefix typically will identify the halogenradical. Thus, for example, the term “perfluoro” means that everyhydrogen radical on the substituent to which the prefix is attached issubstituted with a fluorine radical. To illustrate, the term“perfluoroalkyl” means an alkyl substituent wherein a fluorine radicalis in the place of each hydrogen radical.

The term “carbonyl” (alone or in combination with another term(s)) means—C(O)—.

The term “aminocarbonyl” (alone or in combination with another term(s))means —C(O)—NH₂.

The term “oxo” (alone or in combination with another term(s)) means(═O). —The term “oxy” (alone or in combination with another term(s))means an ether substituent, and may be depicted as —O—.

The term “alkylhydroxy” (alone or in combination with another term(s))means -alkyl-OH.

The term “alkylamino” (alone or in combination with another term(s))means -alkyl-NH₂.

The term “alkyloxy” (alone or in combination with another term(s)) meansan alkylether substituent, i.e., —O-alkyl. Examples of such asubstituent include methoxy (—O—CH₃), ethoxy, n-propoxy, isopropoxy,n-butoxy, iso-butoxy, sec-butoxy, and tert-butoxy.

The term “alkylcarbonyl” (alone or in combination with another term(s))means —C(O)-alkyl.

The term “aminoalkylcarbonyl” (alone or in combination with anotherterm(s)) means —C(O)-alkyl-NH₂.

The term “alkyloxycarbonyl” (alone or in combination with anotherterm(s)) means —C(O)—O-alkyl.

The term “carbocyclylcarbonyl” (alone or in combination with anotherterm(s)) means —C(O)-carbocyclyl.

Similarly, the term “heterocyclylcarbonyl” (alone or in combination withanother term(s)) means —C(O)-heterocyclyl.

The term “carbocyclylalkylcarbonyl” (alone or in combination withanother term(s)) means —C(O)-alkyl-carbocyclyl.

Similarly, the term “heterocyclylalkylcarbonyl” (alone or in combinationwith another term(s)) means —C(O)-alkyl-heterocyclyl.

The term “carbocyclyloxycarbonyl” (alone or in combination with anotherterm(s)) means —C(O)-O-carbocyclyl.

The term “carbocyclylalkyloxycarbonyl” (alone or in combination withanother term(s)) means —C(O)—O-alkyl-carbocyclyl.

The term “thio” or “thia” (alone or in combination with another term(s))means a thiaether substituent, i.e., an ether substituent wherein adivalent sulfur atom is in the place of the ether oxygen atom. Such asubstituent may be depicted as —S—. This, for example,“alkyl-thio-alkyl” means alkyl-S-alkyl (alkyl-sulfanyl-alkyl).

The term “thiol” or “sulfhydryl” (alone or in combination with anotherterm(s)) means a sulfhydryl substituent, and may be depicted as —SH.

The term “(thiocarbonyl)” (alone or in combination with another term(s))means a carbonyl wherein the oxygen atom has been replaced with asulfur. Such a substituent may be depicted as —C(S)—.

The term “sulfonyl” (alone or in combination with another term(s)) means—S(O)₂—.

The term “aminosulfonyl” (alone or in combination with another term(s))means —S(O)₂—NH₂.

The term “sulfinyl” or “sulfoxido” (alone or in combination with anotherterm(s)) means —S(O)—.

The term “heterocyclyl” (alone or in combination with another term(s))means a saturated (i.e., “heterocycloalkyl”), partially saturated (i.e.,“heterocycloalkenyl”), or completely unsaturated (i.e., “heteroaryl”)ring structure containing a total of 3 to 14 ring atoms. At least one ofthe ring atoms is a heteroatom (i.e., oxygen, nitrogen, or sulfur), withthe remaining ring atoms being independently selected from the groupconsisting of carbon, oxygen, nitrogen, and sulfur. A heterocyclyl maybe a single-ring (monocyclic) or polycyclic ring structure.

A heterocyclyl may be a single ring, which typically contains from 3 to7 ring atoms, more typically from 3 to 6 ring atoms, and even moretypically 5 to 6 ring atoms. Examples of single-ring heterocyclylsinclude furanyl, dihydrofuranyl, tetrahydrofuranyl, thiophenyl(thiofuranyl), dihydrothiophenyl, tetrahydrothiophenyl, pyrrolyl,pyrrolinyl, pyrrolidinyl, imidazolyl, imidazolinyl, imidazolidinyl,pyrazolyl, pyrazolinyl, pyrazolidinyl, triazolyl, tetrazolyl, oxazolyl,oxazolidinyl, isoxazolidinyl, isoxazolyl, thiazolyl, isothiazolyl,thiazolinyl, isothiazolinyl, thiazolidinyl, isothiazolidinyl,thiodiazolyl, oxadiazolyl (including 1,2,3-oxadiazolyl,1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl (furazanyl), or 1,3,4-oxadiazolyl),oxatriazolyl (including 1,2,3,4-oxatriazolyl or 1,2,3,5-oxatriazolyl),dioxazolyl (including 1,2,3-dioxazolyl, 1,2,4-dioxazolyl,1,3,2-dioxazolyl, or 1,3,4-dioxazolyl), oxathiazolyl, oxathiolyl,oxathiolanyl, pyranyl, dihydropyranyl, thiopyranyl,tetrahydrothiopyranyl, pyridinyl (azinyl), piperidinyl, diazinyl(including pyridazinyl (1,2-diazinyl), pyrimidinyl (1,3-diazinyl), orpyrazinyl (1,4-diazinyl)), piperazinyl, triazinyl (including1,3,5-triazinyl, 1,2,4-triazinyl, and 1,2,3-triazinyl)), oxazinyl(including 1,2-oxazinyl, 1,3-oxazinyl, or 1,4-oxazinyl)), oxathiazinyl(including 1,2,3-oxathiazinyl, 1,2,4-oxathiazinyl, 1,2,5-oxathiazinyl,or 1,2,6-oxathiazinyl)), oxadiazinyl (including 1,2,3-oxadiazinyl,1,2,4-oxadiazinyl, 1,4,2-oxadiazinyl, or 1,3,5-oxadiazinyl)),morpholinyl, azepinyl, oxepinyl, thiepinyl, and diazepinyl.

A heterocyclyl may alternatively be polycyclic (i.e., may contain morethan one ring). Examples of polycyclic heterocyclyls include bridged,fused, and spirocyclic heterocyclyls. In a spirocyclic heterocyclyl, oneatom is common to two different rings. In a bridged heterocyclyl, therings share at least two common non-adjacent atoms. In a fused-ringheterocyclyl, two or more rings may be fused together, such that tworings share one common bond. Examples of fused ring heterocyclylscontaining two or three rings include indolizinyl, pyranopyrrolyl,4H-quinolizinyl, purinyl, naphthyridinyl, pyridopyridinyl (includingpyrido[3,4-b]-pyridinyl, pyrido[3,2-b]-pyridinyl, orpyrido[4,3-b]-pyridinyl), and pteridinyl. Other examples of fused-ringheterocyclyls include benzo-fused heterocyclyls, such as indolyl,isoindolyl (isobenzazolyl, pseudoisoindolyl), indoleninyl(pseudoindolyl), isoindazolyl (benzpyrazolyl), benzazinyl (includingquinolinyl (1-benzazinyl) or isoquinolinyl (2-benzazinyl)),phthalazinyl, quinoxalinyl, quinazolinyl, benzodiazinyl (includingcinnolinyl (1,2-benzodiazinyl) or quinazolinyl (1,3-benzodiazinyl)),benzopyranyl (including chromanyl or isochromanyl), benzoxazinyl(including 1,3,2-benzoxazinyl, 1,4,2-benzoxazinyl, 2,3,1-benzoxazinyl,or 3,1,4-benzoxazinyl), and benzisoxazinyl (including 1,2-benzisoxazinylor 1,4-benzisoxazinyl).

The term “heteroaryl” (alone or in combination with another term(s))means an aromatic heterocyclyl containing from 5 to 14 ring atoms. Aheteroaryl may be a single ring or 2 or 3 fused rings. Examples ofheteroaryl substituents include 6-membered ring substituents such aspyridyl, pyrazyl, pyrimidinyl, pyridazinyl, and 1,3,5-, 1,2,4- or1,2,3-triazinyl; 5-membered ring substituents such as imidazyl, furanyl,thiophenyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, 1,2,3-, 1,2,4-,1,2,5-, or 1,3,4-oxadiazolyl and isothiazolyl; 6/5-membered fused ringsubstituents such as benzothiofuranyl, benzisoxazolyl, benzoxazolyl,purinyl, and anthranilyl; and 6/6-membered fused rings such asbenzopyranyl, quinolinyl, isoquinolinyl, cinnolinyl, quinazolinyl, andbenzoxazinyl.

A prefix attached to a multi-component substituent only applies to thefirst component. To illustrate, the term “alkylcycloalkyl” contains twocomponents: alkyl and cycloalkyl. Thus, the C₁-C₆- prefix onC₁-C₆-alkylcycloalkyl means that the alkyl component of thealkylcycloalkyl contains from 1 to 6 carbon atoms; the C₁-C₆-prefix doesnot describe the cycloalkyl component. To illustrate further, the prefix“halo” on haloalkyloxyalkyl indicates that only the alkyloxy componentof the alkyloxyalkyl substituent is substituted with one or more halogenradicals. If halogen substitution may alternatively or additionallyoccur on the alkyl component, the substituent would instead be describedas “halogen-substituted alkyloxyalkyl” rather than “haloalkyloxyalkyl.”And finally, if the halogen substitution may only occur on the alkylcomponent, the substituent would instead be described as“alkyloxyhaloalkyl.”

The terms “treat”, “treating” and “treatment” refer to a method ofalleviating or abrogating a disease and/or its attendant symptoms.

The terms “prevent”, “preventing” and “prevention” refer to a method ofpreventing the onset of a disease and/or its attendant symptoms orbarring a subject from acquiring a disease. As used herein, “prevent”,“preventing” and “prevention” also include delaying the onset of adisease and/or its attendant symptoms and reducing a subject's risk ofacquiring a disease.

The term “therapeutically effective amount” refers to that amount of thecompound being administered sufficient to prevent development of oralleviate to some extent one or more of the symptoms of the condition ordisorder being treated.

The term “modulate” refers to the ability of a compound to increase ordecrease the function, or activity, of a kinase. “Modulation”, as usedherein in its various forms, is intended to encompass antagonism,agonism, partial antagonism and/or partial agonism of the activityassociated with kinase. Kinase inhibitors are compounds that, e.g., bindto, partially or totally block stimulation, decrease, prevent, delayactivation, inactivate, desensitize, or down regulate signaltransduction. Kinase activators are compounds that, e.g., bind to,stimulate, increase, open, activate, facilitate, enhance activation,sensitize or up regulate signal transduction.

The term “composition” as used herein is intended to encompass a productcomprising the specified ingredients in the specified amounts, as wellas any product which results, directly or indirectly, from combinationof the specified ingredients in the specified amounts. By“pharmaceutically acceptable” it is meant the carrier, diluent orexcipient must be compatible with the other ingredients of theformulation and not deleterious to the recipient thereof.

The “subject” is defined herein to include animals such as mammals,including, but not limited to, primates (e.g., humans), cows, sheep,goats, horses, dogs, cats, rabbits, rats, mice and the like. Inpreferred embodiments, the subject is a human.

Compounds

In one aspect, the present invention provides compounds of formula (I):

wherein

R^(1a), R^(1b), and R^(1c) are independently hydrogen, hydroxy, nitro,halogen, cyano, trifluoromethyl, trifluoromethoxy, C₁₋₄-alkyl, —OR^(a),—NR^(b)R^(c); —C(O)OR^(a), —C(O)NR^(b)R^(c), —NR^(b)C(O)R^(c),—NHC(O)NHR^(b), or —NHSO₂R^(a);

X is N or CR²;

R² is hydrogen or C₁₋₄-alkyl;

Y is NR³R⁴, NR⁶C(O)R⁷, NR⁶SO₂R⁷, aryl, or heterocyclyl, wherein the aryland heterocyclyl are optionally substituted with one or more R⁵;

R³ is hydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, C₃₋₈-cycloalkyl,C₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, heterocycloalkyl,heterocycloalkyl-(C₁₋₈-alkyl)-, aryl, aryl-(C₁₋₈-alkyl)-, heteroaryl-,or heteroaryl-(C₁₋₈-alkyl), wherein (a) the R³ C₁₋₈-alkyl, C₂₋₈-alkenyl,C₂₋₈-alkynyl substituents, alone or as part of another group, areoptionally substituted with one or more substituents selected from thegroup consisting of halogen, cyano, nitro, —OR^(a), —C(O)R^(a),—C(O)OR^(a), —OC(O)R^(a), —NR^(b)R^(c), —NR^(b)C(O)R^(a),—NHC(O)NHR^(b), —C(O)NR^(b)R^(c), —NHSO₂R^(a), and —SO₂NR^(b)NR^(c); and(b) the R³ C₃₋₈-cycloalkyl, heterocycloalkyl, aryl, and heteroaryl,alone or as part of another group, are optionally substituted with oneor more R⁵;

R⁴ is hydrogen or C₁₋₈-alkyl; wherein the C₁₋₈-alkyl is optionallysubstituted with one or more substituents selected from the groupconsisting of halogen, cyano, —OR^(a), —C(O)R^(a), —C(O)OR^(a),—OC(O)R^(a), —NR^(b)R^(c), —NR^(b)C(O)R^(a), —NHC(O)NHR^(b),—C(O)NR^(b)R^(c), —NHSO₂R^(a), and —SO₂NR^(b)NR^(c);

R⁵ is selected from the group consisting of C₁₋₈-alkyl, C₂₋₈-alkenyl,C₂₋₈-alkynyl, aryl, heterocyclyl, halogen, cyano, nitro, —OR^(d),—C(O)R^(d), —C(O)OR^(d), —OC(O)R^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d),—NHC(O)NHR^(e), —NHSO₂R^(e), —C(O)NR^(e)R^(f), —SR^(d), —S(O)R^(d),—SO₂R^(d), —SO₂NR^(e)NR^(f), —B(OH)₂, —CF₃, —CF₂CF₃, —OCF₃, and —OCF₂CF₃wherein (a) the R⁵ C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, substituentsare optionally substituted with one or more substituents selected fromthe group consisting of aryl, heterocyclyl, C₃₋₈-cycloalkyl, halogen,cyano, nitro, —OR^(d), —C(O)R^(d), —C(O)OR^(d), —OC(O)R^(d),—NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHC(O)NHR^(e), —C(O)NR^(e)R^(f); andwherein (b) the R⁵ aryl or heterocyclyl substituents are optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl,heterocyclyl, halogen, cyano, nitro, —OR^(g), —C(O)R^(g), —C(O)OR^(g),—OC(O)R^(g), —NR^(h)R^(i), —NR^(h)C(O)R^(g), —NHC(O)NHR^(h),—NHSO₂R^(g), —C(O)NR^(h)R^(i), —SR^(g), —S(O)R^(g), —SO₂R^(g),—SO₂NR^(h)NR^(i), —CF₃, —CF₂CF₃, —OCF₃, and —OCF₂CF₃;

R⁶ is hydrogen or C₁₋₈-alkyl;

R⁷ is C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, C₃₋₈-cycloalkyl,C₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, heterocycloalkyl,heterocycloalkyl-(C₁₋₈-alkyl)-, aryl, aryl-(C₁₋₈-alkyl)-, heteroaryl-,or heteroaryl-(C₁₋₈-alkyl)-, wherein (a) the R⁷ C₁₋₈-alkyl,C₂₋₈-alkenyl, C₂₋₈-alkynyl substituents, alone or as part of anothergroup, are optionally substituted with one or more substituents selectedfrom the group consisting of halogen, cyano, nitro, —OR^(a), —C(O)R^(a),—C(O)OR^(a), —OC(O)R^(a), —NR^(b)R^(c), —NR^(b)C(O)R^(a),—NHC(O)NHR^(b), —C(O)NR^(b)R^(c), —NHSO₂R^(a), —SO₂NR^(b)NR^(c), andaryl; and (b) the R⁷ C₃₋₈-cycloalkyl, heterocycloalkyl, aryl, andheteroaryl, alone or as part of another group, are optionallysubstituted with one or more R⁵;

R^(a), at each occurrence, is selected from the group consisting ofhydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,and C₃₋₈-cycloalkyl, wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl are optionally substituted withone or more substituents independently selected from the groupconsisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl, halogen,cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), —O(C₁₋₈-alkyl)NH₂,and —N(C₁₋₈-alkyl)₂;

R^(b) and R^(c), at each occurrence, are independently selected from thegroup consisting of hydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl, and optionally, R^(b) and R^(c)can be joined together to form a 4-7 membered heterocycloalkyl ring,wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,C₃₋₈-cycloalkyl, and 4-7 membered heterocycloalkyl ring are optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl,halogen, cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and—N(C₁₋₈-alkyl)₂;

R^(d), at each occurrence, is selected from the group consisting ofhydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,and C₃₋₈-cycloalkyl, wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl are optionally substituted withone or more substituents independently selected from the groupconsisting of C₁₋₈-alkyl, aryl, aryl-(C₁₋₈-alkyl)-, heterocyclyl,C₃₋₈-cycloalkyl, halogen, cyano, hydroxy, C₁₋₈-alkoxy, —NH₂,—NH(C₁₋₈-alkyl), and —N(C₁₋₈-alkyl)₂; wherein the aryl,aryl-(C₁₋₈-alkyl)-, heterocyclyl, and C₃₋₈-cycloalkyl, alone or as partof another group, are optionally substituted with one or moresubstituents independently selected from the group consisting ofC₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl, halogen, cyano,hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and —N(C₁₋₈-alkyl)₂;

R^(e) and R^(f), at each occurrence, are independently selected from thegroup consisting of hydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl, and optionally, R^(e) and R^(f)can be joined together to form a 4-7 membered heterocycloalkyl ring,wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,C₃₋₈-cycloalkyl, and 4-7 membered heterocycloalkyl ring are optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl,halogen, cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and—N(C₁₋₈-alkyl)₂;

R^(g), at each occurrence, is selected from the group consisting ofhydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,and C₃₋₈-cycloalkyl, wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl are optionally substituted withone or more substituents independently selected from the groupconsisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl, halogen,cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and —N(C₁₋₈-alkyl)₂;

R^(h) and R^(i), at each occurrence, are independently selected from thegroup consisting of hydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl, and optionally, R^(h) and R^(i)can be joined together to form a 4-7 membered heterocycloalkyl ring,wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,C₃₋₈-cycloalkyl, and 4-7 membered heterocycloalkyl ring are optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl,halogen, cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and—N(C₁₋₈-alkyl)₂;

or a pharmaceutically acceptable salt thereof.

In one embodiment of formula (I), R^(1a), R^(1b), and R^(1c) arehydrogen. In another embodiment of formula (I), R^(1b) and R^(1c) arehydrogen and R^(1a) is hydroxy, nitro, halogen, cyano, trifluoromethyl,trifluoromethoxy, C₁₋₄-alkyl, —OR^(a), —NR^(b)R^(c), —C(O)OR^(a),—C(O)NR^(b)R^(c), —NR^(b)C(O)R^(c), —NHC(O)NHR^(b), or —NHSO₂R^(a). Inanother embodiment of formula (I), R^(1a) and R^(1c) are hydrogen andR^(1b) is hydroxy, nitro, halogen, cyano, trifluoromethyl,trifluoromethoxy, C₁₋₄-alkyl, —OR^(a), —NR^(b)R^(c), —C(O)OR^(a),—C(O)NR^(b)R^(c), —NR^(b)C(O)R^(c), —NHC(O)NHR^(b), or —NHSO₂R^(a). Inanother embodiment of formula (I), R^(1c) is hydrogen and R^(1a) andR^(1b) are each independently hydroxy, nitro, halogen, cyano,trifluoromethyl, trifluoromethoxy, C₁₋₄-alkyl, —OR^(a), —NR^(b)R^(c),—C(O)OR^(a), —C(O)NR^(b)R^(c), —NR^(b)C(O)R^(c), —NHC(O)NHR^(b), or—NHSO₂R^(a).

In one embodiment of formula (I), X is N.

In another embodiment of formula (I), X is CR² wherein R² is C₁₋₄-alkyl.In yet another embodiment of formula (I), X is CR² wherein R² ishydrogen.

In one embodiment of formula (I), Y is aryl, which is optionallysubstituted with one or more R⁵. In another embodiment of formula (I),the aryl is unsubstituted. In another embodiment of formula (I), Y isphenyl or naphthyl, and the phenyl or naphthyl is substituted with one,two, or three substituents independently selected from the groupconsisting of C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d),—NR^(e)R^(f), —NR^(c)C(O)R^(d), —NHSO₂R^(c), —SO₂R^(d), —CF₃, and —OCF₃.In another embodiment of formula (I), Y is phenyl, and the phenyl issubstituted with one, two, or three substituents independently selectedfrom the group consisting of C₁₋₈-alkyl, halogen, —OR^(d), —SO₂R^(d),—OCF₃, and —CF₃.

In one embodiment of formula (I), Y is heterocylyl, which is optionallysubstituted with one or more R⁵. In another embodiment of formula (I),the heterocyclyl is unsubstituted. In one embodiment of formula (I), Yis piperidine, thiomorpholine, morpholine, benzodioxolyl, thienyl,pyridinyl, or pyrazolyl, wherein the piperidine, thiomorpholine,morpholine, benzodioxolyl, thienyl, pyridinyl, or pyrazolyl isunsubstituted. In another embodiment of formula (I), Y is piperidine,thiomorpholine, morpholine, benzodioxolyl, thienyl, pyridinyl, orpyrazolyl, and the piperidine, thiomorpholine, morpholine,benzodioxolyl, thienyl, pyridinyl, or pyrazolyl is substituted with one,two, or three substituents independently selected from the groupconsisting of C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d),—NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃.In another embodiment of formula (I), Y is a piperidine, thiomorpholine,morpholine, benzodioxolyl, thienyl, pyridinyl, or pyrazolyl, and thepiperidine, thiomorpholine, morpholine, benzodioxolyl, thienyl,pyridinyl, or pyrazolyl is substituted with one, two, or threesubstituents independently selected from the group consisting ofC₁₋₈-alkyl, halogen, —OR^(d), and —C(O)OR^(d).

In one embodiment of formula (I), Y is heterocycloalkyl, which isoptionally substituted with one or more R⁵. In another embodiment offormula (I), the heterocycloalkyl is unsubsituted. In another embodimentof formula (I), Y is piperidine, thiomorpholine, or morpholine, and thepiperidine, thiomorpholine, or morpholine is unsubstituted. In anotherembodiment of formula (I), the piperidine, thiomorpholine, ormorpholine, is substituted with one, two, or three substituentsindependently selected from the group consisting of C₁₋₈-alkyl,heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), -SO₂R^(d), —CF₃, and —OCF₃. In anotherembodiment of formula (I), Y is a piperidine, thiomorpholine, ormorpholine, and the piperidine, thiomorpholine, or morpholine issubstituted with one, two, or three substituents independently selectedfrom the group consisting of C₁₋₈-alkyl, —OR^(d), and —C(O)OR^(d).

In one embodiment of formula (I), Y is heteroaryl, which is optionallysubstituted with one or more R⁵. In another embodiment of formula (I),the heteroaryl is unsubsituted. In another embodiment, Y is thienyl,pyridinyl, or pyrazolyl, wherein the thienyl, pyridinyl, or pyrazolyl isunsubstituted. In another embodiment of formula (I), the thienyl,pyridinyl, or pyrazolyl is substituted with one, two, or threesubstituents independently selected from the group consisting ofC₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃. In anotherembodiment, Y is thienyl, pyridinyl, or pyrazolyl, and the thienyl,pyridinyl, or pyrazolyl is substituted with one, two, or threesubstituents independently selected from the group consisting of halogenand OR^(d).

In one embodiment of formula (I), Y is NR³R⁴.

In one embodiment of formula (I), R³ is C₁₋₈-alkyl. In anotherembodiment of formula (I), R³ is C₁₋₈-alkyl which is unsubstituted. Inanother embodiment of formula (I), R³ is C₁₋₈-alkyl which is substitutedwith one or more substituents selected from the group consisting ofhalogen, cyano, nitro, —OR^(a), —C(O)R^(a), —C(O)OR^(a), —OC(O)R^(a),—NR^(b)R^(c), —NR^(b)C(O)R^(a), —NHC(O)NHR^(b), —C(O)NR^(b)R^(c),—NHSO₂R^(a), and —SO₂NR^(b)NR^(c). In another embodiment of formula (I),R³ is C₁₋₈-alkyl which is substituted with one or two substituentsselected from the group consisting of —OR^(a), and —NR^(b)R^(c). Inanother embodiment of formula (I), R³ is C₁₋₈-alkyl which is substitutedwith one or two substituents selected from the group consisting of—OR^(a), and —NR^(b)R^(c) wherein R^(a), R^(b), and R^(c) areindependently selected from the group consisting of hydrogen andC₁₋₈-alkyl. In another embodiment of formula (I), R³ is C₁₋₈-alkyl whichis substituted with one or two substituents selected from the groupconsisting of —OH, —OCH₃, —OCH₂CH₂OCH₂CH₂NH₂, and —NHCH₃.

In another embodiment of formula (I), R³ is aryl or heteroaryl, which isoptionally substituted with one or more R⁵. In another embodiment offormula (I), the aryl or heteroaryl is unsubstituted.

In one embodiment of formula (I), R³ is phenyl, which is substitutedwith one, two or three R⁵, and R⁵ is selected from the group consistingof C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d),—NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃,wherein (a) the R⁵ C₁₋₈-alkyl substituent is optionally substituted with—OR^(d). In one embodiment of formula (I), R³ is phenyl, which issubstituted with one, two, or three R⁵, and R⁵ is —OR^(d), wherein R^(d)is C₁₋₈-alkyl.

In another embodiment of formula (I), R³ is a 5-7-membered heteroaryloptionally substituted with one or more R⁵. In another embodiment offormula (I), R³ is 5-7 membered heteroaryl which is unsubstituted. Inyet another embodiment of formula (I), R³ is furanyl, thiophenyl,pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl,isoxazolyl, thiazolyl, isothiazolyl, thiodiazolyl, oxadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, or pyrazinyl, which isunsubstituted. In one embodiment of formula (I), R³ is furanyl,thiophenyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl,oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiodiazolyl,oxadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, or pyrazinyl, which issubstituted with one, two or three R⁵, and R⁵ is selected from the groupconsisting of C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d),—NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃.

In another embodiment of formula (I), R³ is heterocycloalkyl, which isoptionally substituted with one or more R⁵. In another embodiment offormula (I), R³ is heterocycloalkyl, which unsubstituted. In oneembodiment of formula (I), R³ is pyrrolidinyl, tetrhydrofuryl,tetrahydrothienyl, imidazolidinyl, pyrazolidinyl, piperidinyl,tetrahydropyranyl, piperazinyl, dioxanyl, morpholinyl,2-oxopyrrolidinyl, 2,5-dioxopyrrolidinyl, 2-oxopiperidinyl,4-oxopiperidinyl, or 2,6-dioxopiperidinyl, which is unsubstituted. Inone embodiment of formula (I), R⁷ is pyrrolidinyl, tetrhydrofuryl,tetrahydrothienyl, imidazolidinyl, pyrazolidinyl, piperidinyl,tetrahydropyranyl, piperazinyl, dioxanyl, morpholinyl,2-oxopyrrolidinyl, 2,5-dioxopyrrolidinyl, 2-oxopiperidinyl,4-oxopiperidinyl, or 2,6-dioxopiperidinyl, which is substituted withone, two, or three R⁵, and R⁵ is selected from the group consisting ofC₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃, wherein (a)the R⁵ C₁₋₈-alkyl substituent is optionally substituted with —OR^(d). Inone embodiment of formula (I), R³ is pyrrolidinyl, tetrahydrofuryl,piperidinyl, or tetrahydropyranyl.

In another embodiment of formula (I), R³ is cycloalkyl, which isoptionally substituted with one or more R⁵. In another embodiment offormula (I), R³ is cycloalkyl, which unsubstituted. In one embodiment offormula (I), R³ is cyclopentyl, cyclohexyl, and cycloheptyl, which isunsubstituted. In one embodiment of formula (I), R³ is cyclopentyl,cyclohexyl, and cycloheptyl, which is substituted with one, two, orthree R⁵, and R⁵ is selected from the group consisting of C₁₋₈-alkyl,heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃, wherein (a)the R⁵ C₁₋₈-alkyl substituent is optionally substituted with —OR^(d). Inone embodiment of formula (I), R³ is cyclopentyl, cyclohexyl, andcycloheptyl, which is substituted with one, two, or three R⁵, and R⁵ is—OR^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d), or —NHSO₂R^(e), wherein R^(d),at each occurrence, is selected from the group consisting of hydrogen,C₁₋₈-alkyl, heterocyclyl, and C₃₋₈-cycloalkyl, wherein the heterocyclylis optionally substituted with one or more substituents independentlyselected from the group consisting of aryl-(C₁₋₈-alkyl)-, wherein thearyl-(C₁₋₈-alkyl)-, alone or as part of another group, is optionallysubstituted with one or more substituents independently selected fromthe group consisting of halogen, and R^(e) and R^(f), at eachoccurrence, are independently selected from the group consisting ofhydrogen, and C₃₋₈-cycloalkyl.

In one embodiment of formula (I), R³ is C₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-,heterocycloalkyl-(C₁₋₈-alkyl)-, aryl-(C₁₋₈-alkyl)-, orheteroaryl-(C₁₋₈-alkyl)-, and the R³—(C₁₋₈-alkyl)- is unsubstituted. Inanother embodiment of formula (I), where R³ isC₃₋₈-cycloalkyl-(C₁₋₈-alkyl), heterocycloalkyl-(C₁₋₈-alkyl)-,aryl-(C₁₋₈-alkyl)-, or heteroaryl-(C₁₋₈-alkyl)-, the R³ -(C₁₋₈-alkyl)-is optionally substituted with one or two substituents selected from thegroup consisting of —OR^(a) and —NR^(b)R^(c).

In one embodiment of formula (I), R³ is C₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-,heterocycloalkyl-(C₁₋₈-alkyl)-, aryl-(C₁₋₈-alkyl)-, orheteroaryl-(C₁₋₈-alkyl)-, the —(C₁₋₈-alkyl)- is —(C₁-alkyl)-,—(C₂-alkyl)-, or —(C₃-alkyl)-. In one embodiment of formula (I), R³ is—(C₁-alkyl)-.

In another embodiment of formula (I), R³ isC₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, heterocycloalkyl-(C₁₋₈-alkyl)-,aryl-(C₁₋₈-alkyl)-, or heteroaryl-(C₁₋₈-alkyl)-, wherein the R³C₃₋₈-cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionallysubstituted. In another embodiment of formula (I), R³ isC₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, heterocycloalkyl-(C₁₋₈-alkyl)-,aryl-(C₁₋₈-alkyl)-, or heteroaryl-(C₁₋₈-alkyl)-, wherein the R³C₃₋₈-cycloalkyl, heterocycloalkyl, aryl, and heteroaryl areunsubstituted. In another embodiment of formula (I), R³ isC₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, heterocycloalkyl-(C₁₋₈-alkyl)-,aryl-(C₁₋₈-alkyl)-, or heteroaryl-(C₁₋₈-alkyl)-, wherein the R³C₃₋₈-cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are substitutedwith one or more C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d),—C(O)OR^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d),—CF₃, or —OCF₃, wherein (a) the R⁵ C₁₋₈-alkyl substituent is optionallysubstituted with one or more —OR^(d). In another embodiment of formula(I), R³ is C₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-,heterocycloalkyl-(C₁₋₈-alkyl)-, aryl-(C₁₋₈-alkyl)-, orheteroaryl-(C₁₋₈-alkyl)-, wherein the R³ C₃₋₈-cycloalkyl,heterocycloalkyl, aryl, and heteroaryl are substituted with one, two, orthree R⁵, and R⁵ is selected from the group consisting of halogen, —OH,and —CF₃.

In one embodiment of formula (I), R³ is C₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-,the C₃₋₈-cycloalkyl is an optionally substituted cyclobutyl,cyclopentyl, or cyclohexyl.

In one embodiment of formula (I), where R³ isheterocycloalkyl-(C₁₋₈-alkyl)-, the heterocycloalkyl is an optionallysubstituted 5-7 membered heterocycloalkyl. In another embodiment offormula (I), the R³ heterocycicoalkyl is pyrrolidinyl, tetrahydrofuryl,tetrahydrothienyl, imidazolidinyl, pyrazolidinyl, piperidinyl,tetrahydropyranyl, piperazinyl, dioxanyl, morpholinyl,2-oxopyrrolidinyl, 2,5-dioxopyrrolidinyl, 2-oxopiperidinyl,4-oxopiperidinyl, or 2,6-dioxopiperidinyl. In another embodiment offormula (I), wherein R³ is heterocycloalkyl-(C₁₋₈-alkyl)-, theheterocycloalkyl is an optionally substituted pyrrolidinyl,tetrahydrofuryl, piperidinyl, or tetrahydropyranyl.

In one embodiment, wherein R³ is aryl-(C₁₋₈-alkyl)-, the aryl is anoptionally substituted phenyl.

In one embodiment, wherein R³ is heteroaryl-(C₁₋₈-alkyl)-, theheteroaryl is an optionally substituted 5-7-membered heteroaryl. In yetanother embodiment, where R³ is heteroaryl-(C₁₋₈-alkyl)-, the R³hetroaryl is furanyl, thiophenyl, pyrrolyl, imidazolyl, pyrazolyl,triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl,thiodiazolyl, oxadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, orpyrazinyl. In yet another embodiment, where R³ isheteroaryl-(C₁₋₈-alkyl)-, the R³ heteroaryl is imidazolyl.

In one embodiment of formula (I), R⁴ is hydrogen. In another embodimentof formula (I), R⁴ is an unsubstituted branched or straight chain C₁₋₈alkyl. In yet another embodiment of formula (I), R⁴ is methyl, ethyl,propyl, isopropyl, n-butyl, sec-butyl, or t-butyl. In another embodimentof formula (I), R⁴ is methyl. In another embodiment of formula (I), R⁴is a substituted branched or straight chain C₁₋₈ alkyl, wherein theC₁₋₈-alkyl is substituted with —OR^(a) wherein R^(a) is selected fromthe group consisting of H and C₁₋₈-alkyl. In another embodiment offormula (I), R⁴ is a substituted branched or straight chain C₁₋₈ alkyl,wherein the C₁₋₈-alkyl is substituted with —OCH₃.

In another embodiment of formula (I), NR³R⁴ is selected from the groupconsisting of

In another embodiment of formula (I), Y is NR⁶C(O)R⁷ or NR⁶SO₂R⁷.

In one embodiment of formula (I), R⁶ is hydrogen. In another embodimentof formula (I), R⁶ is an unsubstituted branched or straight chainC₁₋₄-alkyl.

In one embodiment of formula (I), R⁷ is optionally substitutedC₁₋₈-alkyl. In one embodiment of formula (I), the R⁷ C₁₋₈-alkyl isunsubstituted. In another embodiment of formula (I), the R⁷ C₁₋₈-alkylis substituted with one or more substituents independently selected fromthe groups consisting of halogen, —OR^(a), —NR^(b)R^(c),—NR^(b)C(O)R^(a), —NHSO₂R^(a), —SO₂NR^(b)NR^(e), and aryl, whereinR^(a), R^(b), and R^(c) are independently selected from the groupconsisting of H and C₁₋₈-alkyl. In another embodiment of formula (I),the R⁷ C₁₋₈-alkyl is optionally substituted with one or two substituentsselected from the group consisting of hydroxy, methoxy, ethoxy, amino,—NHCH₃, —NHCOCH₃, —NHSO₂CH₃, and —SO₂NHCH₃.

In another embodiment of formula (I), R⁷ is aryl or heteroaryl, which isoptionally substituted with one or more R⁵. In another embodiment offormula (I), the aryl or heteroaryl is unsubstituted.

In one embodiment of formula (I), R⁷ is phenyl, which is substitutedwith one, two or three R⁵, and R⁵ is selected from the group consistingof C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d),—NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃,wherein (a) the R⁵ C₁₋₈-alkyl substituent is optionally substituted with-OR^(d). In one embodiment of formula (I), R³ is phenyl, which issubstituted with one, two, or three R⁵, and R⁵ is —OR^(d), wherein R^(d)is C₁₋₈-alkyl.

In another embodiment of formula (I), R⁷ is a 5-7-membered heteroaryloptionally substituted with one or more R⁵. In another embodiment offormula (I), R⁷ is 5-7 membered heteroaryl which is unsubstituted. Inyet another embodiment of formula (I), R⁷ is furanyl, thiophenyl,pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl,isoxazolyl, thiazolyl, isothiazolyl, thiodiazolyl, oxadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, or pyrazinyl, which isunsubstituted. In one embodiment of formula (I), R⁷ is furanyl,thiophenyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl,oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiodiazolyl,oxadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, or pyrazinyl, which issubstituted with one, two or three R⁵, and R⁵ is selected from the groupconsisting of C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d),—NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃.In one embodiment of formula (I), the R⁷ heteroaryl is pyridinyl.

In another embodiment of formula (I), R⁷ is heterocycloalkyl, which isoptionally substituted with one or more R⁵. In another embodiment offormula (I), R⁷ is heterocycloalkyl, which unsubstituted. In oneembodiment of formula (I), R⁷ is pyrrolidinyl, tetrhydrofuryl,tetrahydrothienyl, imidazolidinyl, pyrazolidinyl, piperidinyl,tetrahydropyranyl, piperazinyl, dioxanyl, morpholinyl,2-oxopyrrolidinyl, 2,5-dioxopyrrolidinyl, 2-oxopiperidinyl,4-oxopiperidinyl, or 2,6-dioxopiperidinyl, which is unsubstituted. Inone embodiment of formula (I), R⁷ is pyrrolidinyl, tetrhydrofuryl,tetrahydrothienyl, imidazolidinyl, pyrazolidinyl, piperidinyl,tetrahydropyranyl, piperazinyl, dioxanyl, morpholinyl,2-oxopyrrolidinyl, 2,5-dioxopyrrolidinyl, 2-oxopiperidinyl,4-oxopiperidinyl, or 2,6-dioxopiperidinyl, which is substituted withone, two, or three R⁵, and R⁵ is selected from the group consisting ofC₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃, wherein (a)the R⁵ C₁₋₈-alkyl substituent is optionally substituted with —OR^(d). Inone embodiment of formula (I), R⁷ is pyrrolidinyl, tetrahydrofuryl,piperidinyl, or tetrahydropyranyl.

In another embodiment of formula (I), R⁷ is cycloalkyl, which isoptionally substituted with one or more R⁵. In another embodiment offormula (I), R⁷ is cycloalkyl, which unsubstituted. In one embodiment offormula (I), R⁷ is cyclopentyl, cyclohexyl, and cycloheptyl, which isunsubstituted. In one embodiment of formula (I), R⁷ is cyclopentyl,cyclohexyl, and cycloheptyl, which is substituted with one, two, orthree R⁵, and R⁵ is selected from the group consisting of C₁₋₈-alkyl,heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃, wherein (a)the R⁵ C₁₋₈-alkyl substituent is optionally substituted with —OR^(d). Inone embodiment of formula (I), R⁷ is cyclopentyl, cyclohexyl, andcycloheptyl, which is substituted with one, two, or three R⁵, and R⁵ is—OR^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d), or —NHSO₂R^(e).

In one embodiment of formula (I), R⁷ is C₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-,heterocycloalkyl-(C₁₋₈-alkyl)-, aryl-(C₁₋₈-alkyl)-, orheteroaryl-(C₁₋₈-alkyl)-, and the R⁷—(C₁₋₈-alkyl)- is unsubstituted. Inanother embodiment of formula (I), where R⁷ isC₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, heterocycloalkyl-(C₁₋₈-alkyl)-,aryl-(C₁₋₈-alkyl)-, or heteroaryl-(C₁₋₈-alkyl)-, the R⁷—(C₁₋₈-alkyl)- isoptionally substituted with one or two substituents selected from thegroup consisting of —OR^(a) and —NR^(b)R^(c).

In one embodiment of formula (I), R⁷ is C₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-,heterocycloalkyl-(C₁₋₈-alkyl)-, aryl-(C₁₋₈-alkyl)-, orheteroaryl-(C₁₋₈-alkyl)-, the —(C₁₋₈-alkyl)- is —(C₁-alkyl)-,—(C₂-alkyl)-, or —(C₃-alkyl)-. In one embodiment of formula (I), R⁷ is—(C₁-alkyl)-.

In another embodiment of formula (I), R⁷ isC₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, heterocycloalkyl-(C₁₋₈-alkyl)-,aryl-(C₁₋₈-alkyl)-, or heteroaryl-(C₁₋₈-alkyl)-, wherein the R⁷C₃₋₈-cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionallysubstituted. In another embodiment of formula (I), R⁷ isC₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, heterocycloalkyl-(C₁₋₈-alkyl)-,aryl-(C₁₋₈-alkyl)-, or heteroaryl-(C₁₋₈-alkyl)-, wherein the R⁷C₃₋₈-cycloalkyl, heterocycloalkyl, aryl, and heteroaryl areunsubstituted. In another embodiment of formula (I), R⁷ isC₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, heterocycloalkyl-(C₁₋₈-alkyl)-,aryl-(C₁₋₈-alkyl)-, or heteroaryl-(C₁₋₈-alkyl)-, wherein the R⁷C₃₋₈-cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are substitutedwith one or more C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d),—C(O)OR^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d),—CF₃, or —OCF₃, wherein (a) the R⁵ C₁₋₈-alkyl substituent is optionallysubstituted with one or more —OR^(d). In another embodiment of formula(I), R⁷ is C₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-,heterocycloalkyl-(C₁₋₈-alkyl)-, aryl-(C₁₋₈-alkyl)-, orheteroaryl-(C₁₋₈-alkyl)-, wherein the R³ C₃₋₈-cycloalkyl,heterocycloalkyl, aryl, and heteroaryl are substituted with one, two, orthree R⁵, and R⁵ is selected from the group consisting of halogen, —OH,and —CF₃.

In one embodiment of formula (I), wherein R⁷ isC₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, the C₃₋₈-cycloalkyl is an optionallysubstituted cyclobutyl, cyclopentyl, or cyclohexyl.

In one embodiment of formula (I), where R⁷ isheterocycloalkyl-(C₁₋₈-alkyl)-, the heterocycloalkyl is an optionallysubstituted 5-7 membered heterocycloalkyl. In another embodiment offormula (I), the R⁷ heterocycicoalkyl is pyrrolidinyl, tetrahydrofuryl,tetrahydrothienyl, imidazolidinyl, pyrazolidinyl, piperidinyl,tetrahydropyranyl, piperazinyl, dioxanyl, morpholinyl,2-oxopyrrolidinyl, 2,5-dioxopyrrolidinyl, 2-oxopiperidinyl,4-oxopiperidinyl, or 2,6-dioxopiperidinyl. In another embodiment offormula (I), wherein R⁷ is heterocycloalkyl-(C₁₋₈-alkyl)-, theheterocycloalkyl is an optionally substituted pyrrolidinyl,tetrahydrofuryl, piperidinyl, or tetrahydropyranyl.

In one embodiment, wherein R⁷ is aryl-(C₁₋₈-alkyl)-, the aryl is anoptionally substituted phenyl.

In one embodiment, wherein R⁷ is heteroaryl-(C₁₋₈-alkyl)-, theheteroaryl is an optionally substituted 5-7-membered heteroaryl. In yetanother embodiment, where R⁷ is heteroaryl-(C₁₋₈-alkyl)-, the R⁷hetroaryl is furanyl, thiophenyl, pyrrolyl, imidazolyl, pyrazolyl,triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl,thiodiazolyl, oxadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, orpyrazinyl. In yet another embodiment, where R⁷ isheteroaryl-(C₁₋₈-alkyl)-, the R³ heteroaryl is imidazolyl.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is N, Yis NR³R⁴, wherein R³ is C₃₋₈-cycloalkyl, wherein the C₃₋₈-cycloalkyl isoptionally substituted with one or two substituents independentlyselected from the group consisting of C₁₋₈-alkyl, heterocyclyl, halogen,—OR^(d), —C(O)OR^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e),—SO₂R^(d), —CF₃, and —OCF₃ wherein the C₁₋₈-alkyl is optionallysubstituted with one or more —OR^(d), and wherein R^(d), R^(e), andR^(f) are independently selected from the group consisting of hydrogen,C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is isCR², R² is hydrogen, Y is NR³R⁴, wherein R³ is C₃₋₈-cycloalkyl, whereinthe C₃₋₈-cycloalkyl is optionally substituted with one or twosubstituents independently selected from the group consisting ofC₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃ wherein theC₁₋₈-alkyl is optionally substituted with one or more —OR^(d), whereinR⁴ is hydrogen or C₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) areindependently selected from the group consisting of hydrogen,C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is N, Yis NR³R⁴, wherein R³ is aryl, wherein the aryl is optionally substitutedwith one or two substituents independently selected from the groupconsisting of C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d),—NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃wherein the C₁₋₈-alkyl is optionally substituted with one or more—OR^(d), wherein R⁴ is hydrogen or C₁₋₈-alkyl, and wherein R^(d), R^(e),and R^(f) are independently selected from the group consisting ofhydrogen, C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is isCR², R² is hydrogen, Y is NR³R⁴, wherein R³ is aryl, wherein the aryl isoptionally substituted with one or two substituents independentlyselected from the group consisting of C₁₋₈-alkyl, heterocyclyl, halogen,—OR^(d), —C(O)OR^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e),—SO₂R^(d), —CF₃, and —OCF₃ wherein the C₁₋₈-alkyl is optionallysubstituted with one or more —OR^(d), wherein R⁴ is hydrogen orC₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) are independentlyselected from the group consisting of hydrogen, C₁₋₈-alkyl, andC₃₋₈-cycloalkyl.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is N, Yis NR³R⁴, wherein R³ is aryl-(C₁₋₈-alkyl)-, wherein the aryl isoptionally substituted with one or two substituents independentlyselected from the group consisting of C₁₋₈-alkyl, heterocyclyl, halogen,—OR^(d), —C(O)OR^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e),—SO₂R^(d), —CF₃, and —OCF₃ wherein the C₁₋₈-alkyl is optionallysubstituted with one or more —OR^(d), wherein R⁴ is hydrogen orC₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) are independentlyselected from the group consisting of hydrogen, C₁₋₈-alkyl, andC₃₋₈-cycloalkyl.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is isCR², R² is hydrogen, Y is NR³R⁴, wherein R³ is aryl-(C₁₋₈-alkyl)-,wherein the aryl is optionally substituted with one or two substituentsindependently selected from the group consisting of C₁₋₈-alkyl,heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃ wherein theC₁₋₈-alkyl is optionally substituted with one or more —OR^(d), whereinR⁴ is hydrogen or C₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) areindependently selected from the group consisting of hydrogen,C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is N, Yis NR³R⁴, wherein R³ is heterocycloalkyl, wherein the heterocycloalkylis optionally substituted with one or two substituents independentlyselected from the group consisting of C₁₋₈-alkyl, heterocyclyl, halogen,—OR^(d), —C(O)OR^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e),—SO₂R^(d), —CF₃, and —OCF₃ wherein the C₁₋₈-alkyl is optionallysubstituted with one or more —OR^(d), wherein R⁴ is hydrogen orC₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) are independentlyselected from the group consisting of hydrogen, C₁₋₈-alkyl, andC₃₋₈-cycloalkyl.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is isCR², R² is hydrogen, Y is NR³R⁴, wherein R³ is heterocycloalkyl, whereinthe heterocycloalkyl is optionally substituted with one or twosubstituents independently selected from the group consisting ofC₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃ wherein (a)the C₁₋₈-alkyl is optionally substituted with one or more —OR^(d), and—NHSO₂R^(e), wherein R⁴ is hydrogen or C₁₋₈-alkyl, and wherein R^(d),R^(e), and R^(f) are independently selected from the group consisting ofhydrogen, C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is N, Yis NR³R⁴, wherein R³ is heterocycloalkyl-(C₁₋₈-alkyl)-, wherein theheterocycloalkyl is optionally substituted with one or two substituentsindependently selected from the group consisting of C₁₋₈-alkyl,heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃ wherein theC₁₋₈-alkyl is optionally substituted with one or more —OR^(d), whereinR⁴ is hydrogen or C₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) areindependently selected from the group consisting of hydrogen,C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is isCR², R² is hydrogen, Y is heterocyclyl, wherein the heterocyclyl isoptionally substituted with one or more substituents independentlyselected from the group consisting of C₁₋₈-alkyl, heterocyclyl, halogen,—OR^(d), —C(O)OR^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e),—SO₂R^(d), —CF₃, and —OCF₃ wherein the C₁₋₈-alkyl is optionallysubstituted with one or more —OR^(d), wherein R⁴ is hydrogen orC₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) are independentlyselected from the group consisting of hydrogen, C₁₋₈-alkyl, andC₃₋₈-cycloalkyl.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is N, Yis heterocyclyl, wherein the heterocyclyl is optionally substituted withone or more substituents independently selected from the groupconsisting of C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d),—NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃wherein the C₁₋₈-alkyl is optionally substituted with one or more—OR^(d), wherein R⁴ is hydrogen or C₁₋₈-alkyl, and wherein R^(d), R^(e),and R^(f) are independently selected from the group consisting ofhydrogen, C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is isCR², R² is hydrogen, Y is NR³R⁴, wherein R³ is C₁₋₈-alkyl, wherein theR³ C₁₋₈-alkyl is optionally substituted with one or more substituentsselected from the group consisting of halogen, —OR^(a), and—NR^(b)R^(c);wherein R⁴ is hydrogen or C₁₋₈-alkyl, and wherein R^(c),R^(d), R^(e), and R^(f) are independently selected from the groupconsisting of hydrogen, C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is N, Yis NR³R⁴, wherein R³ is C₁₋₈-alkyl, wherein the R³ C₁₋₈-alkyl isoptionally substituted with one or more substituents selected from thegroup consisting of halogen, —OR^(a), and —NR^(b)R^(c);wherein R⁴ ishydrogen or C₁₋₈-alkyl, and wherein R^(c), R^(d), R^(e), and R^(f) areindependently selected from the group consisting of hydrogen,C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is isCR², R² is hydrogen, Y is NR³R⁴, wherein R³ is C₁₋₈-alkyl, wherein theR³ C₁₋₈-alkyl is optionally substituted with one or more substituentsselected from the group consisting of halogen, —OR^(a), and—NR^(b)R^(c);wherein R⁴ is hydrogen or C₁₋₈-alkyl, wherein theC₁₋₈-alkyl is optionally substituted with one or more substituentsselected from the group consisting of halogen, and —OR^(a), and whereinR^(c), R^(d), R^(e), and R^(f) are independently selected from the groupconsisting of hydrogen, C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is N, Yis NR³R⁴, wherein R³ is C₁₋₈-alkyl, wherein the R³ C₁₋₈-alkyl isoptionally substituted with one or more substituents selected from thegroup consisting of halogen, —OR^(a), and —NR^(b)R^(c);wherein R⁴ ishydrogen or C₁₋₈-alkyl, wherein the C₁₋₈-alkyl is optionally substitutedwith one or more substituents selected from the group consisting ofhalogen, and —OR^(a), and wherein R^(c), R^(d), R^(e), and R^(f) areindependently selected from the group consisting of hydrogen,C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is N, Yis NR³R⁴, wherein R³ is heteroaryl-(C₁₋₈-alkyl)-, wherein the aryl isoptionally substituted with one or two substituents independentlyselected from the group consisting of C₁₋₈-alkyl, heterocyclyl, halogen,—OR^(d), —C(O)OR^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e),—SO₂R^(d), —CF₃, and —OCF₃ wherein the C₁₋₈-alkyl is optionallysubstituted with one or more —OR^(d), wherein R⁴ is hydrogen orC₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) are independentlyselected from the group consisting of hydrogen, C₁₋₈-alkyl, andC₃₋₈-cycloalkyl.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is isCR², R² is hydrogen, Y is NR³R⁴, wherein R³ is heteroaryl-(C₁₋₈-alkyl)-,wherein the aryl is optionally substituted with one or two substituentsindependently selected from the group consisting of C₁₋₈-alkyl,heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃ wherein theC₁₋₈-alkyl is optionally substituted with one or more —OR^(d), whereinR⁴ is hydrogen or C₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) areindependently selected from the group consisting of hydrogen,C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is isCR², R² is hydrogen, Y is NR³R⁴, wherein R³ is C₁₋₈-alkyl, wherein theR³ C₁₋₈-alkyl is optionally substituted with one or more substituentsselected from the group consisting of halogen, —OR^(a), and—NR^(b)R^(c);wherein R⁴ is hydrogen or C₁₋₈-alkyl, wherein theC₁₋₈-alkyl is optionally substituted with one or more substituentsselected from the group consisting of halogen, and —OR^(a), whereinR^(c), R^(d), R^(e), and R^(f) are independently selected from the groupconsisting of hydrogen, C₁₋₈-alkyl, and C₃₋₈-cycloalkyl, wherein theC₁₋₈-alkyl is optionally substituted with —NH₂, or —O(C₁₋₈-alkyl)NH₂.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is N, Yis NR³R⁴, wherein R³ is C₁₋₈-alkyl, wherein the R³ C₁₋₈-alkyl isoptionally substituted with one or more substituents selected from thegroup consisting of halogen, —OR^(a), and —NR^(b)R^(c);wherein R⁴ ishydrogen or C₁₋₈-alkyl, wherein the C₁₋₈-alkyl is optionally substitutedwith one or more substituents selected from the group consisting ofhalogen, and —OR^(a), wherein R^(c), R^(d), R^(e), and R^(f) areindependently selected from the group consisting of hydrogen,C₁₋₈-alkyl, and C₃₋₈-cycloalkyl, wherein the C₁₋₈-alkyl is optionallysubstituted with —NH₂, or —O(C₁₋₈-alkyl)NH₂.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is isCR², R² is hydrogen, Y is aryl, wherein the aryl is optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d),—C(O)OR^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d),—CF₃, and —OCF₃ wherein the C₁₋₈-alkyl is optionally substituted withone or more —OR^(d), wherein R⁴ is hydrogen or C₁₋₈-alkyl, and whereinR^(d), R^(e), and R^(f) are independently selected from the groupconsisting of hydrogen, C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is N, Yis aryl, wherein the aryl is optionally substituted with one or moresubstituents independently selected from the group consisting ofC₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃ wherein theC₁₋₈-alkyl is optionally substituted with one or more —OR^(d), whereinR⁴ is hydrogen or C₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) areindependently selected from the group consisting of hydrogen,C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is isCR², R² is hydrogen, Y is heteroaryl, wherein the heteroaryl isoptionally substituted with one or more substituents independentlyselected from the group consisting of C₁₋₈-alkyl, heterocyclyl, halogen,—OR^(d), —C(O)OR^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e),—SO₂R^(d), —CF₃, and —OCF₃ wherein the C₁₋₈-alkyl is optionallysubstituted with one or more —OR^(d), wherein R⁴ is hydrogen orC₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) are independentlyselected from the group consisting of hydrogen, C₁₋₈-alkyl, andC₃₋₈-cycloalkyl.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is N, Yis heteroaryl, wherein the heteroaryl is optionally substituted with oneor more substituents independently selected from the group consisting ofC₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃ wherein theC₁₋₈-alkyl is optionally substituted with one or more —OR^(d), whereinR⁴ is hydrogen or C₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) areindependently selected from the group consisting of hydrogen,C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b) , and R^(1c) are hydrogen, X is N, Yis NR³R⁴, wherein R³ is C₃₋₈-cycloalkyl, wherein the C₃₋₈-cycloalkyl isoptionally substituted with one or two substituents independentlyselected from the group consisting of C₁₋₈-alkyl, heterocyclyl, halogen,—OR^(d), —C(O)OR^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e),—SO₂R^(d), —CF₃, and —OCF₃ wherein the C₁₋₈-alkyl is optionallysubstituted with one or more —OR^(d), and wherein R^(d), R^(e), andR^(f) are independently selected from the group consisting of hydrogen,C₁₋₈-alkyl, C₃₋₈-cycloalkyl, and heterocyclyl wherein the heterocyclylis optionally substituted with one or more aryl-(C₁₋₈-alkyl)-, whereinthe aryl-(C₁₋₈-alkyl)-, is optionally substituted with one or morehalogen.

In another embodiment, the present invention provides compounds offormula (I) wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is isCR², R² is hydrogen, Y is NR³R⁴, wherein R³ is C₃₋₈-cycloalkyl, whereinthe C₃₋₈-cycloalkyl is optionally substituted with one or twosubstituents independently selected from the group consisting ofC₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃ wherein theC₁₋₈-alkyl is optionally substituted with one or more —OR^(d), whereinR⁴ is hydrogen or C₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) areindependently selected from the group consisting of hydrogen,C₁₋₈-alkyl, and C₃₋₈-cycloalkyl, and heterocyclyl wherein theheterocyclyl is optionally substituted with one or morearyl-(C₁₋₈-alkyl)-, wherein the aryl-(C₁₋₈-alkyl)-, is optionallysubstituted with one or more halogen.

Another aspect of the invention provides compounds of formula (II),wherein R^(1a), R^(1b), R^(1c), R³ and R⁴ are as defined generally andin subsets above.

In one aspect, the present invention provides compounds of formula (II),wherein

R^(1a), R^(1b), and R^(1c) are independently hydrogen, hydroxy, nitro,halogen, cyano, trifluoromethyl, trifluoromethoxy, C₁₋₄-alkyl, —OR^(a),—NR^(b)R^(c); —C(O)OR^(a), —C(O)NR^(b)R^(c), —NR^(b)C(O)R^(c),—NHC(O)NHR^(b), or —NHSO₂R^(a);

R³ is hydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, C₃₋₈-cycloalkyl,C₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, heterocycloalkyl,heterocycloalkyl-(C₁₋₈-alkyl)-, aryl, aryl-(C₁₋₈-alkyl)-, heteroaryl-,or heteroaryl-(C₁₋₈-alkyl)-, wherein (a) the R³ C₁₋₈-alkyl,C₂₋₈-alkenyl, C₂₋₈-alkynyl substituents, alone or as part of anothergroup, are optionally substituted with one or more substituents selectedfrom the group consisting of halogen, cyano, nitro, —OR^(a), —C(O)R^(a),—C(O)OR^(a), —OC(O)R^(a), —NR^(b)R^(c), —NR^(b)C(O)R^(a),—NHC(O)NHR^(b), —C(O)NR^(b)R^(c), —NHSO₂R^(a), —SO₂NR^(b)NR^(c), andaryl; and (b) the R³ C₃₋₈-cycloalkyl, heterocycloalkyl, aryl, andheteroaryl, alone or as part of another group, are optionallysubstituted with one or more R⁵;

R⁴ is hydrogen or C₁₋₈-alkyl; wherein the C₁₋₈-alkyl is optionallysubstituted with one or more substituents selected from the groupconsisting of halogen, cyano, —OR^(a), —C(O)R^(a), —C(O)OR^(a),—OC(O)R^(a), —NR^(b)R^(c), —NR^(b)C(O)R^(a), —NHC(O)NHR^(b),—C(O)NR^(b)R^(c), —NHSO₂R^(a), and —SO₂NR^(b)NR^(c);

R⁵ is selected from the group consisting of C₁₋₈-alkyl, C₂₋₈-alkenyl,C₂₋₈-alkynyl, aryl, heterocyclyl, halogen, cyano, nitro, —OR^(d),—C(O)R^(d), —C(O)OR^(d), —OC(O)R^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d),—NHC(O)NHR^(e), —NHSO₂R^(e), —C(O)NR^(e)R^(f), —SR^(d), —S(O)R^(d),—SO₂R^(d), —SO₂NR^(e)NR^(f), —B(OH)₂, —CF₃, —CF₂CF₃, —OCF₃, and —OCF₂CF₃wherein (a) the R⁵ C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, substituentsare optionally substituted with one or more substituents selected fromthe group consisting of aryl, heterocyclyl, C₃₋₈-cycloalkyl, halogen,cyano, nitro, —OR^(d), —C(O)R^(d), —C(O)OR^(d), —OC(O)R^(d),—NR^(c)R^(f), —NR^(c)C(O)R^(d), —NHC(O)NHR^(c), —C(O)NR^(e)R^(f); andwherein (b) the R⁵ aryl or heterocyclyl substituents are optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl,heterocyclyl, halogen, cyano, nitro, —OR^(g), —C(O)R^(g), —C(O)OR^(g),—OC(O)R^(g), —NR^(h)R^(i), —NR^(h)C(O)R^(g), —NHC(O)NHR^(h),—NHSO₂R^(g), —C(O)NR^(h)R^(i), —SR^(g), —S(O)R^(g), —SO₂R^(g),—SO₂NR^(h)NR^(i), —CF₃, —CF₂CF₃, —OCF₃, and —OCF₂CF₃;

R^(a), at each occurrence, is selected from the group consisting ofhydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,and C₃₋₈-cycloalkyl, wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl are optionally substituted withone or more substituents independently selected from the groupconsisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl, halogen,cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl)-,—O(C₁₋₈-alkyl)NH₂,and —N(C₁₋₈-alkyl)₂;

R^(b) and R^(c), at each occurrence, are independently selected from thegroup consisting of hydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-allcynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl, and optionally, R^(b) and R^(c)can be joined together to form a 4-7 membered heterocycloalkyl ring,wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,C₃₋₈-cycloalkyl, and 4-7 membered heterocycloalkyl ring are optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl,halogen, cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl)-, and—N(C₁₋₈-alkyl)₂;

R^(d), at each occurrence, is selected from the group consisting ofhydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,and C₃₋₈-cycloalkyl, wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl are optionally substituted withone or more substituents independently selected from the groupconsisting of C₁₋₈-alkyl, aryl, aryl-(C₁₋₈-alkyl)-, heterocyclyl,C₃₋₈-cycloalkyl, halogen, cyano, hydroxy, C₁₋₈-alkoxy, —NH₂,—NH(C₁₋₈-alkyl)-, and —N(C₁₋₈-alkyl)₂; wherein the aryl,aryl-(C₁₋₈-alkyl)-, heterocyclyl, and C₃₋₈-cycloalkyl, alone or as partof another group, are optionally substituted with one or moresubstituents independently selected from the group consisting ofC₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl, halogen, cyano,hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and —N(C₁₋₈-alkyl)₂;

R^(e) and R^(f), at each occurrence, are independently selected from thegroup consisting of hydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl, and optionally, R^(e) and R^(f)can be joined together to form a 4-7 membered heterocycloalkyl ring,wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,C₃₋₈-cycloalkyl, and 4-7 membered heterocycloalkyl ring are optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl,halogen, cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and—N(C₁₋₈-alkyl)₂;

R^(g), at each occurrence, is selected from the group consisting ofhydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,and C₃₋₈-cycloalkyl, wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl are optionally substituted withone or more substituents independently selected from the groupconsisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl, halogen,cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and —N(C₁₋₈-alkyl)₂;

R^(h) and R^(i), at each occurrence, are independently selected from thegroup consisting of hydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl, and optionally, R^(h) and R^(i)can be joined together to form a 4-7 membered heterocycloalkyl ring,wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,C₃₋₈-cycloalkyl, and 4-7 membered heterocycloalkyl ring are optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl,halogen, cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and—N(C₁₋₈-alkyl)₂;

or a pharmaceutically acceptable salt thereof.

In one embodiment of formula (II), R^(1a), R^(1b), and R^(1c) arehydrogen. In another embodiment of formula (II), R^(1b) and R^(1c) arehydrogen and R^(1a) is hydroxy, nitro, halogen, cyano, trifluoromethyl,trifluoromethoxy, C₁₋₄-alkyl, —OR^(a), —NR^(b)R^(c), —C(O)OR^(a),—C(O)NR^(b)R^(c), —NR^(b)C(O)R^(c), —NHC(O)NHR^(b), or —NHSO₂R^(a). Inanother embodiment of formula (II), R^(1a) and R^(1c) are hydrogen andR^(1b) is hydroxy, nitro, halogen, cyano, trifluoromethyl,trifluoromethoxy, C₁₋₄-alkyl, —OR^(a), —NR^(b)R^(c), —C(O)OR^(a),—C(O)NR^(b)R^(c), —NR^(b)C(O)R^(c), —NHC(O)NHR^(b), or —NHSO₂R^(a). Inanother embodiment of formula (II), R^(1c) is hydrogen and R^(1a) andR^(1b) are each independently hydroxy, nitro, halogen, cyano,trifluoromethyl, trifluoromethoxy, C₁₋₄-alkyl, —OR^(a), —NR^(b)R^(c),—C(O)OR^(a), —C(O)NR^(b)R^(c), —NR^(b)C(O)R^(c), —NHC(O)NHR^(b), or—NHSO₂R^(a).

In one embodiment of formula (II), R³ is C₁₋₈-alkyl. In anotherembodiment of formula (II), R³ is C₁₋₈-alkyl which is unsubstituted. Inanother embodiment of formula (II), R³ is C₁₋₈-alkyl which issubstituted with one or more substituents selected from the groupconsisting of halogen, cyano, nitro, —OR^(a), —C(O)R^(a), —C(O)OR^(a),—OC(O)R^(a), —NR^(b)R^(c), —NR^(b)C(O)R^(a), —NHC(O)NHR^(b),—C(O)NR^(b)R^(c), —NHSO₂R^(a), and —SO₂NR^(b)NR^(c). In anotherembodiment of formula (II), R³ is C₁₋₈-alkyl which is substituted withone or two substituents selected from the group consisting of —OR^(a),and —NR^(b)R^(c). In another embodiment of formula (II), R³ isC₁₋₈-alkyl which is substituted with one or two substituents selectedfrom the group consisting of —OR^(a), and —NR^(b)R^(c) wherein R^(a),R^(b), and R^(c) are independently selected from the group consisting ofhydrogen and C₁₋₈-alkyl. In another embodiment of formula (II), R³ isC₁₋₈-alkyl which is substituted with one or two substituents selectedfrom the group consisting of —OH, —OCH₃, —OCH₂CH₂OCH₂CH₂NH₂, and —NHCH₃.

In another embodiment of formula (II), R³ is aryl or heteroaryl, whichis optionally substituted with one or more R⁵. In another embodiment offormula (II), the aryl or heteroaryl is unsubstituted.

In one embodiment of formula (II), R³ is phenyl, which is substitutedwith one, two or three R⁵, and R⁵ is selected from the group consistingof C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d),—NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃,wherein (a) the R⁵ C₁₋₈-alkyl substituent is optionally substituted with—OR^(d). In one embodiment of formula (II), R³ is phenyl, which issubstituted with one, two, or three R⁵, and R⁵ is —OR^(d), wherein R^(d)is C₁₋₈-alkyl.

In another embodiment of formula (II), R³ is a 5-7-membered heteroaryloptionally substituted with one or more R⁵. In another embodiment offormula (I), R³ is 5-7 membered heteroaryl which is unsubstituted. Inyet another embodiment of formula (I), R³ is furanyl, thiophenyl,pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl,isoxazolyl, thiazolyl, isothiazolyl, thiodiazolyl, oxadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, or pyrazinyl, which isunsubstituted. In one embodiment of formula (I), R³ is furanyl,thiophenyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl,oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiodiazolyl,oxadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, or pyrazinyl, which issubstituted with one, two or three R⁵, and R⁵ is selected from the groupconsisting of C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d),—NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃.

In another embodiment of formula (II), R³ is heterocycloalkyl, which isoptionally substituted with one or more R⁵. In another embodiment offormula (II), R³ is heterocycloalkyl, which unsubstituted. In oneembodiment of formula (II), R³ is pyrrolidinyl, tetrhydrofuryl,tetrahydrothienyl, imidazolidinyl, pyrazolidinyl, piperidinyl,tetrahydropyranyl, piperazinyl, dioxanyl, morpholinyl,2-oxopyrrolidinyl, 2,5-dioxopyrrolidinyl, 2-oxopiperidinyl,4-oxopiperidinyl, or 2,6-dioxopiperidinyl, which is unsubstituted. Inone embodiment of formula (II), R⁷ is pyrrolidinyl, tetrhydrofuryl,tetrahydrothienyl, imidazolidinyl, pyrazolidinyl, piperidinyl,tetrahydropyranyl, piperazinyl, dioxanyl, morpholinyl,2-oxopyrrolidinyl, 2,5-dioxopyrrolidinyl, 2-oxopiperidinyl,4-oxopiperidinyl, or 2,6-dioxopiperidinyl, which is substituted withone, two, or three R⁵, and R⁵ is selected from the group consisting ofC₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃, wherein (a)the R⁵ C₁₋₈-alkyl substituent is optionally substituted with —OR^(d). Inone embodiment of formula (II), R³ is pyrrolidinyl, tetrahydrofuryl,piperidinyl, or tetrahydropyranyl.

In another embodiment of formula (II), R³ is cycloalkyl, which isoptionally substituted with one or more R⁵. In another embodiment offormula (II), R³ is cycloalkyl, which unsubstituted. In one embodimentof formula (II), R³ is cyclopentyl, cyclohexyl, and cycloheptyl, whichis unsubstituted. In one embodiment of formula (II), R³ is cyclopentyl,cyclohexyl, and cycloheptyl, which is substituted with one, two, orthree R⁵, and R⁵ is selected from the group consisting of C₁₋₈-alkyl,heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃, wherein (a)the R⁵ C₁₋₈-alkyl substituent is optionally substituted with —OR^(d). Inone embodiment of formula (II), R³ is cyclopentyl, cyclohexyl, andcycloheptyl, which is substituted with one, two, or three R⁵, and R⁵ is—OR^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d), or —NHSO₂R^(e), wherein R^(d),at each occurrence, is selected from the group consisting of hydrogen,C₁₋₈-alkyl, heterocyclyl, and C₃₋₈-cycloalkyl, wherein the heterocyclylis optionally substituted with one or more substituents independentlyselected from the group consisting of aryl-(C₁₋₈-alkyl)-, wherein thearyl-(C₁₋₈-alkyl)-, alone or as part of another group, is optionallysubstituted with one or more substituents independently selected fromthe group consisting of halogen, and R^(e) and R^(f), at eachoccurrence, are independently selected from the group consisting ofhydrogen, and C₃₋₈-cycloalkyl.

In one embodiment of formula (II), R³ is C₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-,heterocycloalkyl-(C₁₋₈-alkyl)-, aryl-(C₁₋₈-alkyl)-, orheteroaryl-(C₁₋₈-alkyl)-, and the R³—(C₁₋₈-alkyl)- is unsubstituted. Inanother embodiment of formula (II), where R³ isC₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, heterocycloalkyl-(C₁₋₈-alkyl)-,aryl-(C₁₋₈-alkyl)-, or heteroaryl-(C₁₋₈-alkyl)-, the R³—(C₁₋₈-alkyl)- isoptionally substituted with one or two substituents selected from thegroup consisting of —OR^(a) and —NR^(b)R^(c).

In one embodiment of formula (II), R³ is C₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-,heterocycloalkyl-(C₁₋₈-alkyl)-, aryl-(C₁₋₈-alkyl)-, orheteroaryl-(C₁₋₈-alkyl)-, the —(C₁₋₈-alkyl)- is —(C₁-alkyl)-,—(C₂-alkyl)-, or —(C₃-alkyl)-. In one embodiment of formula (I), R³ is—(C₁-alkyl)-.

In another embodiment of formula (II), R³ isC₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, heterocycloalkyl-(C₁₋₈-alkyl)-,aryl-(C₁₋₈-alkyl)-, or heteroaryl-(C₁₋₈-alkyl)-, wherein the R³C₃₋₈-cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionallysubstituted. In another embodiment of formula (I), R³ isC₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, heterocycloalkyl-(C₁₋₈-alkyl)-,aryl-(C₁₋₈-alkyl)-, or heteroaryl-(C₁₋₈-alkyl)-, wherein the R³C₃₋₈-cycloalkyl, heterocycloalkyl, aryl, and heteroaryl areunsubstituted. In another embodiment of formula (I), R³ isC₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, heterocycloalkyl-(C₁₋₈-alkyl)-,aryl-(C₁₋₈-alkyl)-, or heteroaryl-(C₁₋₈-alkyl)-, wherein the R³C₃₋₈-cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are substitutedwith one or more C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d),—C(O)OR^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d),—CF₃, or —OCF₃, wherein (a) the R⁵ C₁₋₈-alkyl substituent is optionallysubstituted with one or more —OR^(d). In another embodiment of formula(II), R³ is C₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-,heterocycloalkyl-(C₁₋₈-alkyl)-, aryl-(C₁₋₈-alkyl)-, orheteroaryl-(C₁₋₈-alkyl)-, wherein the R³ C₃₋₈-cycloalkyl,heterocycloalkyl, aryl, and heteroaryl are substituted with one, two, orthree R⁵, and R⁵ is selected from the group consisting of halogen, —OH,and —CF₃.

In one embodiment of formula (II), R³ is C₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-,the C₃₋₈-cycloalkyl is an optionally substituted cyclobutyl,cyclopentyl, or cyclohexyl.

In one embodiment of formula (II), where R³ isheterocycloalkyl-(C₁₋₈-alkyl)-, the heterocycloalkyl is an optionallysubstituted 5-7 membered heterocycloalkyl. In another embodiment offormula (II), the R³ heterocycicoalkyl is pyrrolidinyl, tetrahydrofuryl,tetrahydrothienyl, imidazolidinyl, pyrazolidinyl, piperidinyl,tetrahydropyranyl, piperazinyl, dioxanyl, morpholinyl,2-oxopyrrolidinyl, 2,5-dioxopyrrolidinyl, 2-oxopiperidinyl,4-oxopiperidinyl, or 2,6-dioxopiperidinyl. In another embodiment offormula (II), wherein R³ is heterocycloalkyl-(C₁₋₈-alkyl)-, theheterocycloalkyl is an optionally substituted morpholinyl ortetrahydropyranyl.

In one embodiment, wherein R³ is aryl-(C₁₋₈-alkyl)-, the aryl is anoptionally substituted phenyl.

In one embodiment, wherein R³ is heteroaryl-(C₁₋₈-alkyl)-, theheteroaryl is an optionally substituted 5-7-membered heteroaryl. In yetanother embodiment, where R³ is heteroaryl-(C₁₋₈-alkyl)-, the R³hetroaryl is furanyl, thiophenyl, pyrrolyl, imidazolyl, pyrazolyl,triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl,thiodiazolyl, oxadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, orpyrazinyl. In yet another embodiment, where R³ isheteroaryl-(C₁₋₈-alkyl)-, the R³ heteroaryl is imidazolyl.

In one embodiment of formula (II), R⁴ is hydrogen. In another embodimentof formula (II), R⁴ is an unsubstituted branched or straight chain C₁₋₈alkyl. In yet another embodiment of formula (II), R⁴ is methyl, ethyl,propyl, isopropyl, n-butyl, sec-butyl, or t-butyl. In another embodimentof formula (II), R⁴ is methyl. In another embodiment of formula (II), R⁴is a substituted branched or straight chain C₁₋₈ alkyl, wherein theC₁₋₈-alkyl is substituted with —OR^(a) wherein R^(a) is selected fromthe group consisting of H and C₁₋₈-alkyl. In another embodiment offormula (II), R⁴ is a substituted branched or straight chain C₁₋₈ alkyl,wherein the C₁₋₈-alkyl is substituted with —OCH₃.

In another embodiment of formula (II), NR³R⁴ is selected from the groupconsisting of

Another aspect of the invention provides compounds of formula (III),wherein R^(1a), R^(1b), R^(1c), R³ and R⁴ are as defined generally andin subsets above.

In one aspect, the present invention provides compounds of formula(III), wherein

R^(1a), R^(1b), and R^(1c) are independently hydrogen, hydroxy, nitro,halogen, cyano, trifluoromethyl, trifluoromethoxy, C₁₋₄-alkyl, —OR^(a),—NR^(b)R^(c); —C(O)OR^(a), —C(O)NR^(b)R^(c), —NR^(b)C(O)R^(c),—NHC(O)NHR^(b), or —NHSO₂R^(a);

R³ is hydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, C₃₋₈-cycloalkyl,C₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, heterocycloalkyl,heterocycloalkyl-(C₁₋₈-alkyl)-, aryl, aryl-(C₁₋₈-alkyl)-, heteroaryl-,or heteroaryl-(C₁₋₈-alkyl)-, wherein (a) the R³ C₁₋₈-alkyl,C₂₋₈-alkenyl, C₂₋₈-alkynyl substituents, alone or as part of anothergroup, are optionally substituted with one or more substituents selectedfrom the group consisting of halogen, cyano, nitro, —OR^(a), —C(O)R^(a),—C(O)OR^(a), —OC(O)R^(a), —NR^(b)R^(c), —NR^(b)C(O)R^(a),—NHC(O)NHR^(b), —C(O)NR^(b)R^(c), —NHSO₂R^(a), —SO₂NR^(b)NR^(c), andaryl; and (b) the R³ C₃₋₈-cycloalkyl, heterocycloalkyl, aryl, andheteroaryl, alone or as part of another group, are optionallysubstituted with one or more R⁵;

R⁴ is hydrogen or C₁₋₈-alkyl; wherein the C₁₋₈-alkyl is optionallysubstituted with one or more substituents selected from the groupconsisting of halogen, cyano, —OR^(a), —C(O)R^(a), —C(O)OR^(a),—OC(O)R^(a), —NR^(b)R^(c), —NR^(b)C(O)R^(a), —NHC(O)NHR^(b),—C(O)NR^(b)R^(c), —NHSO₂R^(a), and —SO₂NR^(b)NR^(c);

R⁵ is selected from the group consisting of C₁₋₈-alkyl, C₂₋₈-alkenyl,C₂₋₈-alkynyl, aryl, heterocyclyl, halogen, cyano, nitro, —OR^(d),—C(O)R^(d), —C(O)OR^(d), —OC(O)R^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d),—NHC(O)NHR^(e), —NHSO₂R^(e), —C(O)NR^(e)R^(f), —SR^(d), —S(O)R^(d),—SO₂R^(d), —SO₂NR^(e)NR^(f), —B(OH)₂, —CF₃, —CF₂CF₃, —OCF₃, and —OCF₂CF₃wherein (a) the R⁵ C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, substituentsare optionally substituted with one or more substituents selected fromthe group consisting of aryl, heterocyclyl, C₃₋₈-cycloalkyl, halogen,cyano, nitro, —OR^(d), —C(O)R^(d), —C(O)OR^(d), —OC(O)R^(d),—NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHC(O)NHR^(c), —C(O)NR^(e)R^(f); andwherein (b) the R⁵ aryl or heterocyclyl substituents are optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl,heterocyclyl, halogen, cyano, nitro, —OR^(g), —C(O)R^(g), —C(O)OR^(g),—OC(O)R^(g), —NR^(h)R^(i), —NR^(h)C(O)R^(g), —NHC(O)NHR^(h),—NHSO₂R^(g), —C(O)NR^(h)R^(i), —SR^(g), —S(O)R^(g), —SO₂R^(g),—SO₂NR^(h)NR^(i), —CF₃, —CF₂CF₃, —OCF₃, and —OCF₂CF₃;

R^(a), at each occurrence, is selected from the group consisting ofhydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,and C₃₋₈-cycloalkyl, wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl are optionally substituted withone or more substituents independently selected from the groupconsisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl, halogen,cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), —O(C₁₋₈-alkyl)NH₂,and —N(C₁₋₈-alkyl)₂;

R^(b) and R^(c), at each occurrence, are independently selected from thegroup consisting of hydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl, and optionally, R^(b) and R^(c)can be joined together to form a 4-7 membered heterocycloalkyl ring,wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,C₃₋₈-cycloalkyl, and 4-7 membered heterocycloalkyl ring are optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl,halogen, cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and—N(C₁₋₈-alkyl)₂;

R^(d), at each occurrence, is selected from the group consisting ofhydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,and C₃₋₈-cycloalkyl, wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl are optionally substituted withone or more substituents independently selected from the groupconsisting of C₁₋₈-alkyl, aryl, aryl-(C₁₋₈-alkyl)-, heterocyclyl,C₃₋₈-cycloalkyl, halogen, cyano, hydroxy, C₁₋₈-alkoxy, —NH₂,—NH(C₁₋₈-alkyl), and —N(C₁₋₈-alkyl)₂; wherein the aryl,aryl-(C₁₋₈-alkyl)-, heterocyclyl, and C₃₋₈-cycloalkyl, alone or as partof another group, are optionally substituted with one or moresubstituents independently selected from the group consisting ofC₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl, halogen, cyano,hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and —N(C₁₋₈-alkyl)₂;

R^(e) and R^(f), at each occurrence, are independently selected from thegroup consisting of hydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl, and optionally, R^(e) and R^(f)can be joined together to form a 4-7 membered heterocycloalkyl ring,wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,C₃₋₈-cycloalkyl, and 4-7 membered heterocycloalkyl ring are optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl,halogen, cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and—N(C₁₋₈-alkyl)₂;

R^(g), at each occurrence, is selected from the group consisting ofhydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,and C₃₋₈-cycloalkyl, wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl are optionally substituted withone or more substituents independently selected from the groupconsisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl, halogen,cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and —N(C₁₋₈-alkyl)₂;

R^(h) and R^(i), at each occurrence, are independently selected from thegroup consisting of hydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl, and optionally, R^(h) and R^(i)can be joined together to form a 4-7 membered heterocycloalkyl ring,wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,C₃₋₈-cycloalkyl, and 4-7 membered heterocycloalkyl ring are optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl,halogen, cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and—N(C₁₋₈-alkyl)₂;

or a pharmaceutically acceptable salt thereof.

In one embodiment of formula (III), R^(1a), R^(1b), and R^(1c) arehydrogen. In another embodiment of formula (III), R^(1b) and R^(1c) arehydrogen and R^(1a) is hydroxy, nitro, halogen, cyano, trifluoromethyl,trifluoromethoxy, C₁₋₄-alkyl, —OR^(a), —NR^(b)R^(c), —C(O)OR^(a),—C(O)NR^(b)R^(c), —NR^(b)C(O)R^(c), —NHC(O)NHR^(b), or —NHSO₂R^(a). Inanother embodiment of formula (III), R^(1a) and R^(1c) are hydrogen andR^(1b) is hydroxy, nitro, halogen, cyano, trifluoromethyl,trifluoromethoxy, C₁₋₄-alkyl, —OR^(a), —NR^(b)R^(c), —C(O)OR^(a),—C(O)NR^(b)R^(c), —NR^(b)C(O)R^(c), —NHC(O)NHR^(b), or —NHSO₂R^(a). Inanother embodiment of formula (III), R^(1c) is hydrogen and R^(1a) andR^(1b) are each independently hydroxy, nitro, halogen, cyano,trifluoromethyl, trifluoromethoxy, C₁₋₄-alkyl, —OR^(a), —NR^(b)R^(c),—C(O)OR^(a), —C(O)NR^(b)R^(c), —NR^(b)C(O)R^(c), —NHC(O)NHR^(b), or—NHSO₂R^(a).

In one embodiment of formula (III), R³ is C₁₋₈-alkyl. In anotherembodiment of formula (III), R³ is C₁₋₈-alkyl which is unsubstituted. Inanother embodiment of formula (III), R³ is C₁₋₈-alkyl which issubstituted with one or more substituents selected from the groupconsisting of halogen, cyano, nitro, —OR^(a), —C(O)R^(a), —C(O)OR^(a),—OC(O)R^(a), —NR^(b)R^(c), —NR^(b)C(O)R^(a), —NHC(O)NHR^(b),—C(O)NR^(b)R^(c), —NHSO₂R^(a), and —SO₂NR^(b)NR^(c). In anotherembodiment of formula (I), R³ is C₁₋₈-alkyl which is substituted withone or two substituents selected from the group consisting of —OR^(a),and —NR^(b)R^(c). In another embodiment of formula (III), R³ isC₁₋₈-alkyl which is substituted with one or two substituents selectedfrom the group consisting of —OR^(a), and —NR^(b)R^(c) wherein R^(a),R^(b), and R^(c) are independently selected from the group consisting ofhydrogen and C₁₋₈-alkyl. In another embodiment of formula (III), R³ isC₁₋₈-alkyl which is substituted with one or two substituents selectedfrom the group consisting of —OH, —OCH₃, —OCH₂CH₂OCH₂CH₂NH₂, and —NHCH₃.

In another embodiment of formula (III), R³ is aryl or heteroaryl, whichis optionally substituted with one or more R⁵. In another embodiment offormula (III), the aryl or heteroaryl is unsubstituted.

In one embodiment of formula (III), R³ is phenyl, which is substitutedwith one, two or three R⁵, and R⁵ is selected from the group consistingof C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d),—NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃,wherein (a) the R⁵ C₁₋₈-alkyl substituent is optionally substituted with—OR^(d). In one embodiment of formula (III), R³ is phenyl, which issubstituted with one, two, or three R⁵, and R⁵ is —OR^(d), wherein R^(d)is C₁₋₈-alkyl.

In another embodiment of formula (III), R³ is a 5-7-membered heteroaryloptionally substituted with one or more R⁵. In another embodiment offormula (III), R³ is 5-7 membered heteroaryl which is unsubstituted. Inyet another embodiment of formula (III), R³ is furanyl, thiophenyl,pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl,isoxazolyl, thiazolyl, isothiazolyl, thiodiazolyl, oxadiazolyl,pyridinyl, pyridazinyl, pyrimidinyl, or pyrazinyl, which isunsubstituted. In one embodiment of formula (III), R³ is furanyl,thiophenyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl,oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, thiodiazolyl,oxadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, or pyrazinyl, which issubstituted with one, two or three R⁵, and R⁵ is selected from the groupconsisting of C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d),—NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃.

In another embodiment of formula (III), R³ is heterocycloalkyl, which isoptionally substituted with one or more R⁵. In another embodiment offormula (III), R³ is heterocycloalkyl, which unsubstituted. In oneembodiment of formula (III), R³ is pyrrolidinyl, tetrhydrofuryl,tetrahydrothienyl, imidazolidinyl, pyrazolidinyl, piperidinyl,tetrahydropyranyl, piperazinyl, dioxanyl, morpholinyl,2-oxopyrrolidinyl, 2,5-dioxopyrrolidinyl, 2-oxopiperidinyl,4-oxopiperidinyl, or 2,6-dioxopiperidinyl, which is unsubstituted. Inone embodiment of formula (III), R⁷ is pyrrolidinyl, tetrhydrofuryl,tetrahydrothienyl, imidazolidinyl, pyrazolidinyl, piperidinyl,tetrahydropyranyl, piperazinyl, dioxanyl, morpholinyl,2-oxopyrrolidinyl, 2,5-dioxopyrrolidinyl, 2-oxopiperidinyl,4-oxopiperidinyl, or 2,6-dioxopiperidinyl., which is substituted withone, two, or three R⁵, and R⁵ is selected from the group consisting ofC₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃, wherein (a)the R⁵ C₁₋₈-alkyl substituent is optionally substituted with —OR^(d). Inone embodiment of formula (III), R³ is pyrrolidinyl, tetrahydrofuryl,piperidinyl, or tetrahydropyranyl.

In another embodiment of formula (III), R³ is cycloalkyl, which isoptionally substituted with one or more R⁵. In another embodiment offormula (III), R³ is cycloalkyl, which unsubstituted. In one embodimentof formula (III), R³ is cyclopentyl, cyclohexyl, and cycloheptyl, whichis unsubstituted. In one embodiment of formula (III), R³ is cyclopentyl,cyclohexyl, and cycloheptyl, which is substituted with one, two, orthree R⁵, and R⁵ is selected from the group consisting of C₁₋₈-alkyl,heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃, wherein (a)the R⁵ C₁₋₈-alkyl substituent is optionally substituted with —OR^(d). Inone embodiment of formula (III), R³ is cyclopentyl, cyclohexyl, andcycloheptyl, which is substituted with one, two, or three R⁵, and R⁵ is—OR^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d), or —NHSO₂R^(e), wherein R^(d),at each occurrence, is selected from the group consisting of hydrogen,C₁₋₈-alkyl, heterocyclyl, and C₃₋₈-cycloalkyl, wherein the heterocyclylis optionally substituted with one or more substituents independentlyselected from the group consisting of aryl-(C₁₋₈-alkyl)-, wherein thearyl-(C₁₋₈-alkyl)-, alone or as part of another group, is optionallysubstituted with one or more substituents independently selected fromthe group consisting of halogen, and R^(e) and R^(f), at eachoccurrence, are independently selected from the group consisting ofhydrogen, and C₃₋₈-cycloalkyl.

In one embodiment of formula (III), R³ is C₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-,heterocycloalkyl-(C₁₋₈-alkyl)-, aryl-(C₁₋₈-alkyl)-, orheteroaryl-(C₁₋₈-alkyl)-, and the R³—(C₁₋₈-alkyl)- is unsubstituted. Inanother embodiment of formula (III), where R³ isC₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, heterocycloalkyl-(C₁₋₈-alkyl)-,aryl-(C₁₋₈-alkyl)-, or heteroaryl-(C₁₋₈-alkyl)-, the R³—(C₁₋₈-alkyl)- isoptionally substituted with one or two substituents selected from thegroup consisting of —OR^(a)and —NR^(b)R^(c).

In one embodiment of formula (III), R³ is C₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-,heterocycloalkyl-(C₁₋₈-alkyl)-, aryl-(C₁₋₈-alkyl)-, orheteroaryl-(C₁₋₈-alkyl)-, the —(C₁₋₈-alkyl)- is —(C₁-alkyl)-,—(C₂-alkyl)-, or —(C₃-alkyl)-. In one embodiment of formula (III), R³ is—(C₁-alkyl)-.

In another embodiment of formula (III), R³ isC₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, heterocycloalkyl-(C₁₋₈-alkyl)-,aryl-(C₁₋₈-alkyl)-, or heteroaryl-(C₁₋₈-alkyl)-, wherein the R³C₃₋₈-cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionallysubstituted. In another embodiment of formula (III), R³ isC₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, heterocycloalkyl-(C₁₋₈-alkyl)-,aryl-(C₁₋₈-alkyl)-, or heteroaryl-(C₁₋₈-alkyl)-, wherein the R³C₃₋₈-cycloalkyl, heterocycloalkyl, aryl, and heteroaryl areunsubstituted. In another embodiment of formula (III), R³ isC₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, heterocycloalkyl-(C₁₋₈-alkyl)-,aryl-(C₁₋₈-alkyl)-, or heteroaryl-(C₁₋₈-alkyl)-, wherein the R³C₃₋₈-cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are substitutedwith one or more C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d),—C(O)OR^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d),—CF₃, or —OCF₃, wherein (a) the R⁵ C₁₋₈-alkyl substituent is optionallysubstituted with one or more —OR^(d). In another embodiment of formula(III), R³ is C₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-,heterocycloalkyl-(C₁₋₈-alkyl)-, aryl-(C₁₋₈-alkyl)-, orheteroaryl-(C₁₋₈-alkyl)-, wherein the R³ C₃₋₈-cycloalkyl,heterocycloalkyl, aryl, and heteroaryl are substituted with one, two, orthree R⁵, and R⁵ is selected from the group consisting of halogen, —OH,and —CF₃.

In one embodiment of formula (III), R³ is C₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-,the C₃₋₈-cycloalkyl is an optionally substituted cyclobutyl,cyclopentyl, or cyclohexyl.

In one embodiment of formula (III), where R³ isheterocycloalkyl-(C₁₋₈-alkyl)-, the heterocycloalkyl is an optionallysubstituted 5-7 membered heterocycloalkyl. In another embodiment offormula (III), the R³ heterocycicoalkyl is pyrrolidinyl,tetrahydrofuryl, tetrahydrothienyl, imidazolidinyl, pyrazolidinyl,piperidinyl, tetrahydropyranyl, piperazinyl, dioxanyl, morpholinyl,2-oxopyrrolidinyl, 2,5-dioxopyrrolidinyl, 2-oxopiperidinyl,4-oxopiperidinyl, or 2,6-dioxopiperidinyl. In another embodiment offormula (I), wherein R³ is heterocycloalkyl-(C₁₋₈-alkyl)-, theheterocycloalkyl is an optionally substituted morpholinyl ortetrahydropyranyl.

In one embodiment, wherein R³ is aryl-(C₁₋₈-alkyl)-, the aryl is anoptionally substituted phenyl.

In one embodiment, wherein R³ is heteroaryl-(C₁₋₈-alkyl)-, theheteroaryl is an optionally substituted 5-7-membered heteroaryl. In yetanother embodiment, where R³ is heteroaryl-(C₁₋₈-alkyl)-, the R³hetroaryl is furanyl, thiophenyl, pyrrolyl, imidazolyl, pyrazolyl,triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl,thiodiazolyl, oxadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, orpyrazinyl. In yet another embodiment, where R³ isheteroaryl-(C₁₋₈-alkyl)-, the R³ heteroaryl is imidazolyl.

In one embodiment of formula (III), R⁴ is hydrogen. In anotherembodiment of formula (III), R⁴ is an unsubstituted branched or straightchain C₁₋₈ alkyl. In yet another embodiment of formula (III), R⁴ ismethyl, ethyl, propyl, isopropyl, n-butyl, sec-butyl, or t-butyl. Inanother embodiment of formula (III), R⁴ is methyl. In another embodimentof formula (II), R⁴ is a substituted branched or straight chain C₁₋₈alkyl, wherein the C₁₋₈-alkyl is substituted with —OR^(a) wherein R^(a)is selected from the group consisting of H and C₁₋₈-alkyl. In anotherembodiment of formula (III), R⁴ is a substituted branched or straightchain C₁₋₈ alkyl, wherein the C₁₋₈-alkyl is substituted with —OCH₃.

In another embodiment of formula (III), NR³R⁴ is selected from the groupconsisting of

Another aspect of the invention provides compounds of formula (IV),wherein X, R^(1a), R^(1b), R^(1c), and R⁵ are as defined generally andin subsets above, and n is 0. 1. 2, 3, 4, or 5.

I In one aspect, the present invention provides compounds of formula(IV), wherein

X is N or CR²;

R² is hydrogen or C₁₋₄-alkyl;

R^(1a), R^(1b), and R^(1c) are independently hydrogen, hydroxy, nitro,halogen, cyano, trifluoromethyl, trifluoromethoxy, C₁₋₄-alkyl, —OR^(a),—NR^(b)R^(c); —C(O)OR^(a), —C(O)NR^(b)R^(c), —NR^(b)C(O)R^(c),—NHC(O)NHR^(b), or —NHSO₂R^(a);

n is 0, 1, 2, 3, 4, or 5;

R⁵ is selected from the group consisting of C₁₋₈-alkyl, C₂₋₈-alkenyl,C₂₋₈-alkynyl, aryl, heterocyclyl, halogen, cyano, nitro, —OR^(d),—C(O)R^(d), —C(O)OR^(d), —OC(O)R^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d),—NHC(O)NHR^(e), —NHSO₂R^(e), —C(O)NR^(e)R^(f), —SR^(d), —S(O)R^(d),—SO₂R^(d), —SO₂NR^(e)NR^(f), —B(OH)₂, —CF₃, —CF₂CF₃, —OCF₃, and —OCF₂CF₃wherein (a) the R⁵ C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, substituentsare optionally substituted with one or more substituents selected fromthe group consisting of aryl, heterocyclyl, C₃₋₈-cycloalkyl, halogen,cyano, nitro, —OR^(d), —C(O)R^(d), —C(O)OR^(d), —OC(O)R^(d),—NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHC(O)NHR^(e), —C(O)NR^(e)R^(f); andwherein (b) the R⁵ aryl or heterocyclyl substituents are optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl,heterocyclyl, halogen, cyano, nitro, —OR^(g), —C(O)R^(g), —C(O)OR^(g),—OC(O)R^(g), —NR^(h)R^(i), —NR^(h)C(O)R^(g), —NHC(O)NHR^(h),—NHSO₂R^(g), —C(O)NR^(h)R^(i), —SR^(g), —S(O)R^(g), —SO₂R^(g),—SO₂NR^(h)NR^(i), —CF₃, —CF₂CF₃, —OCF₃, and —OCF₂CF₃;

R^(a), at each occurrence, is selected from the group consisting ofhydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,and C₃₋₈-cycloalkyl, wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl are optionally substituted withone or more substituents independently selected from the groupconsisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl, halogen,cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), —O(C₁₋₈-alkyl)NH₂,and —N(C₁₋₈-alkyl)₂;

R^(b) and R^(c), at each occurrence, are independently selected from thegroup consisting of hydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl, and optionally, R^(b) and R^(c)can be joined together to form a 4-7 membered heterocycloalkyl ring,wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,C₃₋₈-cycloalkyl, and 4-7 membered heterocycloalkyl ring are optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl,halogen, cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and—N(C₁₋₈-alkyl)₂;

R^(d), at each occurrence, is selected from the group consisting ofhydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,and C₃₋₈-cycloalkyl, wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl are optionally substituted withone or more substituents independently selected from the groupconsisting of C₁₋₈-alkyl, aryl, aryl-(C₁₋₈-alkyl)-, heterocyclyl,C₃₋₈-cycloalkyl, halogen, cyano, hydroxy, C₁₋₈-alkoxy, —NH₂,—NH(C₁₋₈-alkyl), and —N(C₁₋₈-alkyl)₂; wherein the aryl,aryl-(C₁₋₈-alkyl)-, heterocyclyl, and C₃₋₈-cycloalkyl, alone or as partof another group, are optionally substituted with one or moresubstituents independently selected from the group consisting ofC₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl, halogen, cyano,hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and —N(C₁₋₈-alkyl)₂;

R^(e) and R^(f), at each occurrence, are independently selected from thegroup consisting of hydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl, and optionally, R^(e) and R^(f)can be joined together to form a 4-7 membered heterocycloalkyl ring,wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,C₃₋₈-cycloalkyl, and 4-7 membered heterocycloalkyl ring are optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl,halogen, cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and—N(C₁₋₈-alkyl)₂;

R^(g), at each occurrence, is selected from the group consisting ofhydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,and C₃₋₈-cycloalkyl, wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl are optionally substituted withone or more substituents independently selected from the groupconsisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl, halogen,cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and —N(C₁₋₈-alkyl)₂;

R^(h) and R^(i), at each occurrence, are independently selected from thegroup consisting of hydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,aryl, heterocyclyl, and C₃₋₈-cycloalkyl, and optionally, R^(h) and R^(i)can be joined together to form a 4-7 membered heterocycloalkyl ring,wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,C₃₋₈-cycloalkyl, and 4-7 membered heterocycloalkyl ring are optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl,halogen, cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and—N(C₁₋₈-alkyl)₂;

or a pharmaceutically acceptable salt thereof.

In one embodiment of formula (IV), R^(1a), R^(1b), and R^(1c) arehydrogen. In another embodiment of formula (IV), R^(1b) and R^(1c) arehydrogen and R^(1a) is hydroxy, nitro, halogen, cyano, trifluoromethyl,trifluoromethoxy, C₁₋₄-alkyl, —OR^(a), —NR^(b)R^(c), —C(O)OR^(a),—C(O)NR^(b)R^(c), —NR^(b)C(O)R^(e), —NHC(O)NHR^(b), or —NHSO₂R^(a). Inanother embodiment of formula (IV), R^(1a) and R^(1c) are hydrogen andR^(1b) is hydroxy, nitro, halogen, cyano, trifluoromethyl,trifluoromethoxy, C₁₋₄-alkyl, —OR^(a), —NR^(b)R^(c), —C(O)OR^(a),—C(O)NR^(b)R^(c), —NR^(b)C(O)R^(c), —NHC(O)NHR^(b), or —NHSO₂R^(a). Inanother embodiment of formula (IV), R^(1c) is hydrogen and R^(1a) andR^(1b) are each independently hydroxy, nitro, halogen, cyano,trifluoromethyl, trifluoromethoxy, C₁₋₄-alkyl, —OR^(a), —NR^(b)R^(c),—C(O)OR^(a), —C(O)NR^(b)R^(c), —NR^(b)C(O)R^(c), —NHC(O)NHR^(b), or—NHSO₂R^(a).

In one embodiment of formula (IV), X is N.

In another embodiment of formula (IV), X is CR² wherein R² isC₁₋₄-alkyl. In yet another embodiment of formula (IV), X is CR² whereinR² is hydrogen.

In another embodiment of formula (IV), n is 0. In another embodiment offormula (IV), n is 1. In another embodiment of formula (IV), n is 2. Inanother embodiment of formula (IV), n is 3.

In another embodiment of formula (IV), R⁵ is selected from the groupconsisting of C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl,heterocyclyl, halogen, oxo, cyano, nitro, —OR^(d), —C(O)R^(d),—C(O)OR^(d), —OC(O)R^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d),—NHC(O)NHR^(e), —NHSO₂R^(e), —C(O)NR^(e)R^(f), —SR^(d), —S(O)R^(d),—SO₂R^(d), —SO₂NR^(e)NR^(f), —B(OH)₂, —CF₃, —CF₂CF₃, —OCF₃, and —OCF₂CF₃wherein (a) the R⁵ C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, substituentsare optionally substituted with one or more substituents selected fromthe group consisting of aryl, heterocyclyl, C₃₋₈-cycloalkyl, halogen,cyano, nitro, oxo, —OR^(d), —C(O)R^(d), —C(O)OR^(d), —OC(O)R^(d),—NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHC(O)NHR^(e), —C(O)NR^(e)R^(f); andwherein (b) the R⁵ aryl or heterocyclyl substituents are optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl,heterocyclyl, halogen, cyano, nitro, oxo —OR^(g), —C(O)R^(g),—C(O)OR^(g), —OC(O)R^(g), —NR^(h)R^(i), —NR^(h)C(O)R^(g),—NHC(O)NHR^(h), —NHSO₂R^(g), —C(O)NR^(h)R^(i), —SR^(g), —S(O)R^(g),—SO₂R^(g), —SO₂NR^(h)NR^(i), —CF₃, —CF₂CF₃, —OCF₃, and —OCF₂CF₃. Inanother embodiment of formula (IV), R⁵ is selected from the groupconsisting of C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d),—NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃,wherein the R⁵ C₁₋₈-alkyl, is optionally substituted with one or more—OR^(d). In another embodiment of formula (IV), R⁵ is selected from thegroup consisting of C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d),—C(O)OR^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d),—CF₃, and —OCF₃, wherein the R⁵ C₁₋₈-alkyl, is optionally substitutedwith one or more —OR^(d), R^(d), at each occurrence, is selected fromthe group consisting of hydrogen, C₁₋₈-alkyl, heterocyclyl, andC₃₋₈-cycloalkyl, wherein the heterocyclyl is optionally substituted withone or more substituents independently selected from the groupconsisting of aryl-(C₁₋₈-alkyl)-, wherein the aryl-(C₁₋₈-alkyl)-, isoptionally substituted with one or more halogen, and R^(e) and R^(f), ateach occurrence, are independently selected from the group consisting ofhydrogen, and C₃₋₈-cycloalkyl.

Specific embodiments contemplated as part of the invention include, butare not limited to, compounds of formula (I), for example:

-   2-(cyclohexylamino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-(benzylamino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-anilino-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-[(trans-4-aminocyclohexyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-[(3,5-difluorobenzyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-(piperidin-4-ylamino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-(4-hydroxypiperidin-1-yl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-{[(1S)-1-phenylethyl]amino}-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   6-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(tetrahydro-2H-pyran-4-ylamino)pyrimidin-4(3H)-one;-   6-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[(tetrahydrofuran-2-ylmethyl)amino]pyrimidin-4(3H)-one;-   2-[cyclohexyl(methyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-{[(1R)-1-phenylethyl]amino}-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-[(2-aminocyclohexyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-(cycloheptylamino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   6-(1H-pyrrolo [2,3 -b]pyridin-3    -yl)-2-(thiomorpholin-4-yl)pyrimidin-4(3H)-one;-   2-{[2-(methylamino)ethyl]amino}-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-[bis(2-methoxyethyl)amino]-6-(1H-pyrrolo    [2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-[(2-methoxyethyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-[(2-hydroxyethyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   6-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-{[2-(trifluoromethyl)benzyl]aminolpyrimidin-4(3)-one;-   2-[4-(hydroxymethyl)piperidin-1-yl]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-{[3-(morpholin-4-yl)propyl]amino}-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-[(3-hydroxybenzyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-(morpholin-4-yl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   1-[6-oxo-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,6-dihydropyrimidin-2-yl]piperidine-4-carboxylic    acid;-   2-(cyclopentylamino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-(4-methoxypiperidin-1-yl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-[(2-hydroxycyclohexyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-[(1-methylpiperidin-4-yl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-{[3-(1H-imidazol-1-yl)propyl]amino}-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-({2-[2-(2-aminoethoxy)ethoxy]ethyl}amino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-phenyl-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-(2-methylphenyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   6-phenyl-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;-   4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-6-[3-(trifluoromethoxy)phenyl]pyridin-2(1H)-one;-   4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-6-[3-(trifluoromethyl)phenyl]pyridin-2(1H)-one;-   6-(2,3-dimethylphenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;-   6-(2-methylphenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;-   6-(1,3-benzodioxol-5-yl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;-   4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-6-(3-thienyl)pyridin-2(1H)-one;-   6-(2-naphthyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;-   6-(3-chlorophenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;-   6-(2,3-dimethoxyphenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;-   6-(2-fluoro-3-methoxyphenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;-   6-(4-chloro-2-fluorophenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;-   6-[2-methoxy-5-(trifluoromethyl)phenyl]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;-   2′-methoxy-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2,3′-bipyridin-6(1H)-one;-   6-(3-chloro-2-methylphenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;-   3′-chloro-2′-methoxy-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2,4′-bipyridin-6(1H)-one;-   6-[3-(morpholin-4-yl)phenyl]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;-   6-[3-(methylsulfonyl)phenyl]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;-   6-(1H-pyrazol-4-yl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;-   2′-methyl-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2,3′-bipyridin-6(1H)-one;-   6-[(3-methoxyphenyl)amino]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;-   6-anilino-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;-   6-[(trans-4-aminocyclohexyl)amino]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;-   N-(trans-4-{[6-oxo-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,6-dihydropyridin-2-yl]amino}cyclohexyl)cyclopropanesulfonamide;-   N-(trans-4-{[6-oxo-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,6-dihydropyridin-2-yl]amino}cyclohexyl)cyclopropanecarboxamide;-   1-(4-fluorobenzyl)-N-(trans-4-{[6-oxo-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,6-dihydropyridin-2-yl]amino}cyclohexyl)azetidine-3-carboxamide;-   2-(4-methylphenyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-(3-methylphenyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;-   2-(2,3-dimethylphenyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;    and-   2-{[3-(3-aminopropoxy)benzyl]amino}-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one.

Compounds of this invention may contain asymmetrically substitutedcarbon atoms in the R or S configuration, wherein the terms “R” and “S”are as defined in Pure Appl. Chem. (1976) 45, 13-10. Compounds havingasymmetrically substituted carbon atoms with equal amounts of R and Sconfigurations are racemic at those atoms. Atoms having excess of oneconfiguration over the other are assigned the configuration in excess,preferably an excess of about 85%-90%, more preferably an excess ofabout 95%-99%, and still more preferably an excess greater than about99%. Accordingly, this invention is meant to embrace racemic mixturesand relative and absolute diastereoisomers of the compounds thereof.

Compounds of this invention may also contain carbon-carbon double bondsor carbon-nitrogen double bonds in the E or Z configuration, wherein theterm “E” represents higher order substituents on opposite sides of thecarbon-carbon or carbon-nitrogen double bond and the term “Z” representshigher order substituents on the same side of the carbon-carbon orcarbon-nitrogen double bond as determined by the Cahn-Ingold-PrelogPriority Rules. The compounds of this invention may also exist as amixture of “E” and “Z” isomers.

Additional geometric isomers may exist in the present compounds. Forexample, the invention contemplates the various geometric isomers andmixtures thereof resulting from the disposition of substituents around acycloalkyl group or a heterocycle group. Substituents around acycloalkyl or a heterocycle are designated as being of cis or transconfiguration.

Compounds of this invention may also exist as tautomers or equilibriummixtures thereof wherein a proton of a compound shifts from one atom toanother. Examples of tautomers include, but are not limited to,keto-enol, phenol-keto, oxime-nitroso, nitro-acid, imine-enamine and thelike. Both tautomeric forms are intended to be encompassed by the scopeof this invention, even though only one tautomeric form may be depicted.For example, compounds of formula (I) may tautomerise into compounds ofthe following structure:

This invention also is directed, in part, to all salts of the compoundsof formula (I). A salt of a compound may be advantageous due to one ormore of the salt's properties, such as, for example, enhancedpharmaceutical stability in differing temperatures and humidities, or adesirable solubility in water or other solvents. Where a salt isintended to be administered to a patient (as opposed to, for example,being in use in an in vitro context), the salt preferably ispharmaceutically acceptable and/or physiologically compatible. The term“pharmaceutically acceptable” is used adjectivally in this patentapplication to mean that the modified noun is appropriate for use as apharmaceutical product or as a part of a pharmaceutical product.Pharmaceutically acceptable salts include salts commonly used to formalkali metal salts and to form addition salts of free acids or freebases. In general, these salts typically may be prepared by conventionalmeans by reacting, for example, the appropriate acid or base with acompound of the invention.

Pharmaceutically acceptable acid addition salts of the compounds offormula (I) can be prepared from an inorganic or organic acid. Examplesof often suitable inorganic acids include hydrochloric, hydrobromic,hydroiodic, nitric, carbonic, sulfuric, and phosphoric acid. Suitableorganic acids generally include, for example, aliphatic, cycloaliphatic,aromatic, araliphatic, heterocyclic, carboxylic, and sulfonic classes oforganic acids. Specific examples of often suitable organic acids includeacetate, trifluoroacetate, formate, propionate, succinate, glycolate,gluconate, digluconate, lactate, malate, tartaric acid, citrate,ascorbate, glucuronate, maleate, fumarate, pyruvate, aspartate,glutamate, benzoate, anthranilic acid, mesylate, stearate, salicylate,p-hydroxybenzoate, phenylacetate, mandelate, embonate (pamoate),ethanesulfonate, benzenesulfonate, pantothenate,2-hydroxyethanesulfonate, sulfanilate, cyclohexylaminosulfonate, algenicacid, beta-hydroxybutyric acid, galactarate, galacturonate, adipate,alginate, bisulfate, butyrate, camphorate, camphorsulfonate,cyclopentanepropionate, dodecylsulfate, glycoheptanoate,glycerophosphate, heptanoate, hexanoate, nicotinate, oxalate, palmoate,pectinate, 2-naphthalesulfonate, 3-phenylpropionate, picrate, pivalate,thiocyanate, tosylate, and undecanoate.

Pharmaceutically acceptable base addition salts of the compounds offormula (I) include, for example, metallic salts and organic salts.Preferred metallic salts include alkali metal (group Ia) salts, alkalineearth metal (group IIa) salts, and other physiologically acceptablemetal salts. Such salts may be made from aluminum, calcium, lithium,magnesium, potassium, sodium, and zinc. Preferred organic salts can bemade from amines, such as tromethamine, diethylamine,N,N′-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine,ethylenediamine, meglumine (N-methylglucamine), and procaine. Basicnitrogen-containing groups can be quaternized with agents such as loweralkyl (C₁-C₆) halides (e.g., methyl, ethyl, propyl, and butyl chlorides,bromides, and iodides), dialkyl sulfates (e.g., dimethyl, diethyl,dibutyl, and diamyl sulfates), long chain halides (e.g., decyl, lauryl,myristyl, and stearyl chlorides, bromides, and iodides), arylalkylhalides (e.g., benzyl and phenethyl bromides), and others.

Compounds of formula (I) (and salts thereof) with any level of purity(including pure and substantially pure) are within the scope ofApplicants' invention. The term “substantially pure” in reference to acompound/salt/isomer, means that the preparation/composition containingthe compound/salt/isomer contains more than about 85% by weight of thecompound/salt/isomer, preferably more than about 90% by weight of thecompound/salt/isomer, preferably more than about 95% by weight of thecompound/salt/isomer, preferably more than about 97% by weight of thecompound/salt/isomer, and preferably more than about 99% by weight ofthe compound/salt/isomer.

Preparation of Compounds

Compounds of this invention may be made by synthetic chemical processes,examples of which are shown herein. It is meant to be understood thatthe order of the steps in the processes may be varied, that reagents,solvents and reaction conditions may be substituted for thosespecifically mentioned, and that vulnerable moieties may be protectedand deprotected, as necessary.

Protecting groups for C(O)OH moieties include, but are not limited to,acetoxymethyl, allyl, benzoylmethyl, benzyl, benzyloxymethyl,tert-butyl, tert-butyldiphenylsilyl, diphenylmethyl, cyclobutyl,cyclohexyl, cyclopentyl, cyclopropyl, diphenylmethylsilyl, ethyl,para-methoxybenzyl, methoxymethyl, methoxyethoxymethyl, methyl,methylthiomethyl, naphthyl, para-nitrobenzyl, phenyl, n-propyl,2,2,2-trichloroethyl, triethylsilyl, 2-(trimethylsilyl)ethyl,2-(trimethylsilyl)ethoxymethyl, triphenylmethyl and the like. Protectinggroups for C(O) and C(O)H moieties include, but are not limited to,1,3-dioxylketal, diethylketal, dimethylketal, 1,3-dithianylketal,O-methyloxime, O-phenyloxime and the like.

Protecting groups for NH moieties include, but are not limited to,acetyl, alanyl, benzoyl, benzyl (phenylmethyl), benzylidene,benzyloxycarbonyl (Cbz), tert-butoxycarbonyl (Boc),3,4-dimethoxybenzyloxycarbonyl, diphenylmethyl, diphenylphosphoryl,formyl, methanesulfonyl, para-methoxybenzyloxycarbonyl, phenylacetyl,phthaloyl, succinyl, trichloroethoxycarbonyl, triethylsilyl,trifluoroacetyl, trimethylsilyl, triphenylmethyl, triphenylsilyl,para-toluenesulfonyl and the like.

Protecting groups for OH and SH moieties include, but are not limitedto, acetyl, allyl, allyloxycarbonyl, benzyloxycarbonyl (Cbz), benzoyl,benzyl, tert-butyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl,3,4-dimethoxybenzyl, 3,4-dimethoxybenzyloxycarbonyl,1,1-dimethyl-2-propenyl, diphenylmethyl, formyl, methanesulfonyl,methoxyacetyl, 4-methoxybenzyloxycarbonyl, para-methoxybenzyl,methoxycarbonyl, methyl, para-toluenesulfonyl,2,2,2-trichloroethoxycarbonyl, 2,2,2-trichloroethyl, triethylsilyl,trifluoroacetyl, 2-(trimethylsilyl)ethoxycarbonyl,2-trimethylsilylethyl, triphenylmethyl,2-(triphenylphosphonio)ethoxycarbonyl and the like.

The present compounds may be prepared by a variety of processes wellknown for the preparation of compounds of this class. For example, thecompounds of formula (I) wherein the groups X, Y, R^(1a), R^(1b), andR^(1c) have the meanings as set forth in the summary unless otherwisenoted, can be synthesized according to the general methods described inSchemes 1-5, using appropriate starting materials by methods generallyavailable to one of ordinary skill in the art.

Abbreviations which have been used in the descriptions of the Schemesand the Examples that follow are: DMF for N,N-dimethylformamide, DMSOfor dimethyl sulfoxide, DMSO-d₆ for deuteriated dimethyl sulfoxide, DMEfor dimethoxyethane, dppf for 1,1′-bis(diphenylphosphino)ferrocene, Et₂Ofor diethyl ether, EtOAc for ethyl acetate, Et₃N for triethylamine, Tsfor toluene sulfonyl, and THF for tetrahydrofuran.

Schemes Schemes

Compounds of formula (2) wherein R^(1a), R^(1b), and R^(1c) are asdescribed for formula (I) herein and PG is a suitable protecting groupsuch as a benzenesulfonyl group, can be treated with compounds offormula (1) wherein X is N or CR²; to provide compounds of formula (3)as shown in Scheme 1. The reaction is typically performed in thepresence of a palladium catalyst and a base at elevated temperature(e.g. at about 70° C. to about 150° C. or optionally under microwaveirradiation) and in a suitable solvent such as DMF, dioxane, ethanol,water, DME, or mixtures thereof. Non-limiting examples of suitablepalladium catalysts include dichlorobis(triphenylphosphine) palladium(II), PdCl₂(dppf)₂, and tetrakis(triphenylphosphine) palladium. Suitablebases include, but are not limited to, cesium fluoride, sodiumcarbonate, potassium acetate, cesium carbonate. Oxidation of themethylthio functionality in compounds of formula (3) with an oxidizingagent such as, but not limited to, OXONE® in a suitable solvent such asmethanol/H₂O or ethyl acetate/H₂O provides compounds of formula (4).

Displacement of the methylsulfonyl group of compounds of formula (4)with amines of formula N(H)R³R⁴, wherein R³ and R⁴ are as described forformula (I) herein, will provide compounds of formula (5). The reactioncan be conducted in a suitable solvent (e.g. dioxane) or in excess ofthe amine employed, at a temperature from about 60° C. to about 150° C.,optionally in the presence of a base (e.g. triethylamine, ordiisopropylethyl amine) and optionally under microwave irradiation.Compounds of formula (6), which are representative of compounds of thisinvention, can be prepared by reacting compounds of formula (5) with anaqueous base such as but not limited to sodium hydroxide or potassiumhydroxide in a solvent such as but not limited to dioxane, or ethanol toremove the protecting group, followed by a work-up and subsequenttreatment with an acid such but not limited to aqueous HCl.

As shown in Scheme 2, compounds of formula (4) can be reacted with aGrignard reagent of formula (7) wherein Y is as aryl or heterocyclyl andX¹ is a halogen such as I, Br, or Cl or a pseudohalide such as atriflate. The Grignard reagent is typically added at low temperature,followed by the addition of an aqueous base such as but not limited tosodium hydroxide at ambient temperature. Addition of an acid such as butnot limited to hydrochloric acid at an elevated temperature will providecompounds of formula (9), which are representative of the compounds ofthis invention.

As shown in Scheme 3, compounds of formula (11) can be prepared fromcompounds of formula (10) by treating the latter with potassiumtert-butoxide at reflux. Compounds of formula (12), wherein R^(1a),R^(1b), and R^(1c) are as described for formula (I) herein, can bereacted with compounds of formula (11) to provide compounds of formula(13). The reaction is typically performed in the presence of a palladiumcatalyst and a base at elevated temperature (e.g. at about 70° C. toabout 150° C. or optionally under microwave irradiation) and in asuitable solvent such as DMF, dioxane, ethanol, water, DME, or mixturesthereof. Non-limiting examples of suitable palladium catalysts includedichlorobis(triphenylphosphine) palladium (II), PdCl₂(dppf)₂, andtetrakis(triphenylphosphine) palladium. Suitable bases include, but arenot limited to, sodium carbonate, potassium acetate, cesium carbonate.Removal of the benzenesulfonyl group from compounds of formula (13) withan aqueous base such as but not limited to sodium hydroxide or potassiumhydroxide, will provide compounds of formula (14). The reaction istypically performed at an elevated temperature and may include anadditional solvent such as but not limited to dioxane or ethanol.Compounds of formula (14) can be reacted with a boronic acid (Y—B(OH)₂)or a boron-ester wherein Y is aryl or heteroaryl, to provide compoundsof formula (15). The reaction is typically performed in the presence ofa palladium catalyst and a base at elevated temperature (e.g. at about70° C. to about 150° C. or optionally under microwave irradiation) andin a suitable solvent such as DMF, dioxane, ethanol, water, DME, ormixtures thereof. Non-limiting examples of suitable palladium catalystsinclude dichlorobis(triphenylphosphine) palladium (II), PdCl₂(dppf)₂,and tetrakis(triphenylphosphine) palladium. Suitable bases include, butare not limited to, cesium fluoride, sodium carbonate, potassiumacetate, cesium carbonate. Addition of an acid such as but not limitedto trifluoroacetic acid at ambient or an elevated temperature willprovide compounds of formula (16), which are representative of compoundsof this invention.

As shown in Scheme 4, direct displacement of the chloro in compounds offormula (13) with amines of formula N(H)R³R⁴ will provide compounds offormula (17). The reaction can be conducted in a suitable solvent (e.g.dioxane) or in excess of the amines employed, at a temperature fromabout 60° C. to about 150° C., optionally in the presence of a base(e.g. triethylamine, diisopropylethyl amine) and optionally undermicrowave irradiation. Addition of an acid such as but not limited top-toluenesulfonic acid will provide compounds of formula (18), which arerepresentative of compounds of this invention.

As shown in scheme 5, 2,6-difluoro-4-iodopyridine can be reacted withcompounds of formula (12) to provide compounds of formula (17). Thereaction is typically performed in the presence of a palladium catalystand a base at elevated temperature (e.g. at about 70° C. to about 150°C. or optionally under microwave irradiation) and in a suitable solventsuch as DMF, dioxane, ethanol, water, DME, or mixtures thereof.Non-limiting examples of suitable palladium catalysts includedichlorobis(triphenylphosphine) palladium (II), PdCl₂(dppf)₂, andtetrakis(triphenylphosphine) palladium. Suitable bases include, but arenot limited to, sodium carbonate, potassium acetate, cesium carbonate.Removal of the benzenesulfonyl group from compounds of formula (17) withan aqueous base such as but not limited to sodium hydroxide or potassiumhydroxide, will provide compounds of formula (18). The reaction istypically performed at an elevated temperature and may include anadditional solvent such as but not limited to dioxane or ethanol.Displacement of the fluoro in compounds of formula (18) withtrans-cyclohexane-1,4-diamine, will provide compounds of formula (19).The reaction is typically performed under microwave irradiation in asolvent such as but not limited to ethanol. Compounds of formula (19)can be heated using microwave irradiation with an aqueous acid such asbut not limited to hydrochloric acid in a solvent such as but notlimited to tert-butanol to provide compounds of formula (20). Compoundsof formula (21), which are representative of compounds of thisinvention, can be prepared by reacting compounds of formula (20) byreacting the latter with compounds of formula R^(f)SO₂Cl, R^(f)C(O)H,R^(f)C(O)OH, R^(f)C(O)Cl or R^(f)C(O)OH under suitable coupling orreduction amination reaction conditions described herein, known to thoseskilled in the art, and readily available in the literature.

Unless otherwise noted, microwave reactions described herein werecarried out either in a Biotage Initiator 8 or in a CEM Explorer at 200W. All reverse-phase HPLC purifications were carried out using a ZorbaxC-18, 250×2.54 column and a eluting with a 0-100% gradient of mobilephase A (0.1% trifluoroacetic acid (TFA) in water) and mobile phase B(0.1% TFA in CH₃CN).

Compositions

In another aspect, the present invention provides pharmaceuticalcompositions for modulating kinase activity in a humans and animals thatwill typically contain a compound of formula (I) and a pharmaceuticallyacceptable carrier.

Compounds having formula (I) may be administered, for example, bucally,ophthalmically, orally, osmotically, parenterally (intramuscularly,intraperintoneally intrasternally, intravenously, subcutaneously),rectally, topically, transdermally, vaginally and intraarterially aswell as by intraarticular injection, infusion, and placement in thebody, such as, for example, the vasculature.

Compounds having formula (I) may be administered with or without anexcipient. Excipients include, but are not limited to, encapsulators andadditives such as absorption accelerators, antioxidants, binders,buffers, coating agents, coloring agents, diluents, disintegratingagents, emulsifiers, extenders, fillers, flavoring agents, humectants,lubricants, perfumes, preservatives, propellants, releasing agents,sterilizing agents, sweeteners, solubilizers, wetting agents, mixturesthereof and the like.

Excipients for preparation of compositions comprising a compound havingformula (I) to be administered orally include, but are not limited to,agar, alginic acid, aluminum hydroxide, benzyl alcohol, benzyl benzoate,1,3-butylene glycol, carbomers, castor oil, cellulose, celluloseacetate, cocoa butter, corn starch, corn oil, cottonseed oil,cross-povidone, diglycerides, ethanol, ethyl cellulose, ethyl laureate,ethyl oleate, fatty acid esters, gelatin, germ oil, glucose, glycerol,groundnut oil, hydroxypropylmethyl celluose, isopropanol, isotonicsaline, lactose, magnesium hydroxide, magnesium stearate, malt,mannitol, monoglycerides, olive oil, peanut oil, potassium phosphatesalts, potato starch, povidone, propylene glycol, Ringer's solution,safflower oil, sesame oil, sodium carboxymethyl cellulose, sodiumphosphate salts, sodium lauryl sulfate, sodium sorbitol, soybean oil,stearic acids, stearyl fumarate, sucrose, surfactants, talc, tragacanth,tetrahydrofurfuryl alcohol, triglycerides, water, mixtures thereof andthe like. Excipients for preparation of compositions comprising acompound having formula (I) to be administered ophthalmically or orallyinclude, but are not limited to, 1,3-butylene glycol, castor oil, cornoil, cottonseed oil, ethanol, fatty acid esters of sorbitan, germ oil,groundnut oil, glycerol, isopropanol, olive oil, polyethylene glycols,propylene glycol, sesame oil, water, mixtures thereof and the like.Excipients for preparation of compositions comprising a compound havingformula (I) to be administered osmotically include, but are not limitedto, chlorofluorohydrocarbons, ethanol, water, mixtures thereof and thelike. Excipients for preparation of compositions comprising a compoundhaving formula (I) to be administered parenterally include, but are notlimited to, 1,3-butanediol, castor oil, corn oil, cottonseed oil,dextrose, germ oil, groundnut oil, liposomes, oleic acid, olive oil,peanut oil, Ringer's solution, safflower oil, sesame oil, soybean oil,U.S.P. or isotonic sodium chloride solution, water, mixtures thereof andthe like. Excipients for preparation of compositions comprising acompound having formula (I) to be administered rectally or vaginallyinclude, but are not limited to, cocoa butter, polyethylene glycol, wax,mixtures thereof and the like.

The pharmaceutical composition and the method of the present inventionmay further comprise other therapeutically active compounds as notedherein which are usually applied in the treatment of the above-mentionedpathological conditions.

Methods of Use

In another aspect, the present invention provides methods of using acompound or composition of the invention to treat or prevent a diseaseor condition involving mediation, overexpression or disregulation ofkinases in a mammal In particular, compounds of this invention areexpected to have utility in treatment of diseases or conditions duringwhich protein kinases such as any or all CDC-7 family members areexpressed.

In one group of embodiments, diseases and conditions of humans or otheranimals that can be treated with inhibitors of kinases, include, but arenot limited to, acoustic neuroma, acute leukemia, acute lymphocyticleukemia, acute myelocytic leukemia (monocytic, myeloblastic,adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic andpromyelocytic), acute t-cell leukemia, basal cell carcinoma, bile ductcarcinoma, bladder cancer, brain cancer, breast cancer, bronchogeniccarcinoma, cervical cancer, chondrosarcoma, chordoma, choriocarcinoma,chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic(granulocytic) leukemia, chronic myleogeneous leukemia, colon cancer,colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse largeB-cell lymphoma, dysproliferative changes (dysplasias and metaplasias),embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma,epithelial carcinoma, erythroleukemia, esophageal cancer,estrogen-receptor positive breast cancer, essential thrombocythemia,Ewing's tumor, fibrosarcoma, follicular lymphoma, germ cell testicularcancer, glioma, heavy chain disease, hemangioblastoma, hepatoma,hepatocellular cancer, hormone insensitive prostate cancer,leiomyosarcoma, liposarcoma, lung cancer, lymphagioendotheliosarcoma,lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin's andnon-Hodgkin's), malignancies and hyperproliferative disorders of thebladder, breast, colon, lung, ovaries, pancreas, prostate, skin anduterus, lymphoid malignancies of T-cell or B-cell origin, leukemia,lymphoma, medullary carcinoma, medulloblastoma, melanoma, meningioma,mesothelioma, multiple myeloma, myelogenous leukemia, myeloma,myxosarcoma, neuroblastoma, non-small cell lung cancer,oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer,pancreatic cancer, papillary adenocarcinomas, papillary carcinoma,pinealoma, polycythemia vera, prostate cancer, rectal cancer, renal cellcarcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous glandcarcinoma, seminoma, skin cancer, small cell lung carcinoma, solidtumors (carcinomas and sarcomas), small cell lung cancer, stomachcancer, squamous cell carcinoma, synovioma, sweat gland carcinoma,thyroid cancer, Waldenström's macroglobulinemia, testicular tumors,uterine cancer and Wilms' tumor.

The methods of the present invention typically involve administering toa subject in need of therapeutic treatment an effective amount of acompound of formula (I). Therapeutically effective amounts of a compoundhaving formula (I) depend on recipient of treatment, disease treated andseverity thereof, composition comprising it, time of administration,route of administration, duration of treatment, potency, rate ofclearance and whether or not another drug is co-administered. The amountof a compound having formula (I) used to make a composition to beadministered daily to a patient in a single dose or in divided doses isfrom about 0.03 to about 200 mg/kg body weight. Single dose compositionscontain these amounts or a combination of submultiples thereof.

Combination Therapy

The present invention further provides methods of using a compound orcomposition of the invention in combination with one or more additionalactive agents.

Compounds having Formula (I) are expected to be useful when used withalkylating agents, angiogenesis inhibitors, antibodies, antimetabolites,antimitotics, antiproliferatives, antivirals, aurora kinase inhibitors,apoptosis promoters (for example, Bcl-xL, Bcl-w and Bfl-l) inhibitors,activators of death receptor pathway, Bcr-Abl kinase inhibitors, BiTE(Bi-Specific T cell Engager) antibodies, antibody drug conjugates,biologic response modifiers, cyclin-dependent kinase inhibitors, cellcycle inhibitors, cyclooxygenase-2 inhibitors, DVDs, leukemia viraloncogene homolog (ErbB2) receptor inhibitors, growth factor inhibitors,heat shock protein (HSP)-90 inhibitors, histone deacetylase (HDAC)inhibitors, hormonal therapies, immunologicals, inhibitors of inhibitorsof apoptosis proteins (IAPs), intercalating antibiotics, kinaseinhibitors, kinesin inhibitors, Jak2 inhibitors, mammalian target ofrapamycin inhibitors, microRNA's, mitogen-activated extracellularsignal-regulated kinase inhibitors, multivalent binding proteins,non-steroidal anti-inflammatory drugs (NSAIDs), poly ADP (adenosinediphosphate)-ribose polymerase (PARP) inhibitors, platinumchemotherapeutics, polo-like kinase (Plk) inhibitors, phosphoinositide-3kinase (PI3K) inhibitors, proteosome inhibitors, purine analogs,pyrimidine analogs, receptor tyrosine kinase inhibitors,etinoids/deltoids plant alkaloids, small inhibitory ribonucleic acids(siRNAs), topoisomerase inhibitors, ubiquitin ligase inhibitors, and thelike, and in combination with one or more of these agents.

BiTE antibodies are bi-specific antibodies that direct T-cells to attackcancer cells by simultaneously binding the two cells. The T-cell thenattacks the target cancer cell. Examples of BiTE antibodies includeadecatumumab (Micromet MT201), blinatumomab (Micromet MT103) and thelike. Without being limited by theory, one of the mechanisms by whichT-cells elicit apoptosis of the target cancer cell is by exocytosis ofcytolytic granule components, which include perforin and granzyme B. Inthis regard, Bcl-2 has been shown to attenuate the induction ofapoptosis by both perforin and granzyme B. These data suggest thatinhibition of Bcl-2 could enhance the cytotoxic effects elicited byT-cells when targeted to cancer cells (V. R. Sutton, D. L. Vaux and J.A. Trapani, J. of Immunology 1997, 158 (12), 5783).

SiRNAs are molecules having endogenous RNA bases or chemically modifiednucleotides. The modifications do not abolish cellular activity, butrather impart increased stability and/or increased cellular potency.Examples of chemical modifications include phosphorothioate groups,2′-deoxynucleotide, 2′-OCH₃-containing ribonucleotides,2′-F-ribonucleotides, 2′-methoxyethyl ribonucleotides, combinationsthereof and the like. The siRNA can have varying lengths (e.g., 10-200bps) and structures (e.g., hairpins, single/double strands, bulges,nicks/gaps, mismatches) and are processed in cells to provide activegene silencing. A double-stranded siRNA (dsRNA) can have the same numberof nucleotides on each strand (blunt ends) or asymmetric ends(overhangs). The overhang of 1-2 nucleotides can be present on the senseand/or the antisense strand, as well as present on the 5′- and/ or the3′-ends of a given strand. For example, siRNAs targeting Mcl-1 have beenshown to enhance the activity of ABT-263, (i.e.,N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-en-1-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzenesulfonamide)or ABT-737 (i.e.,N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide)in multiple tumor cell lines (Tse et. al, Cancer Research 2008, 68(9),3421 and references therein).

Multivalent binding proteins are binding proteins comprising two or moreantigen binding sites. Multivalent binding proteins are engineered tohave the three or more antigen binding sites and are generally notnaturally occurring antibodies. The term “multispecific binding protein”means a binding protein capable of binding two or more related orunrelated targets. Dual variable domain (DVD) binding proteins aretetravalent or multivalent binding proteins binding proteins comprisingtwo or more antigen binding sites. Such DVDs may be monospecific (i.e.,capable of binding one antigen) or multispecific (i.e., capable ofbinding two or more antigens). DVD binding proteins comprising two heavychain DVD polypeptides and two light chain DVD polypeptides are referredto as DVD Ig's. Each half of a DVD Ig comprises a heavy chain DVDpolypeptide, a light chain DVD polypeptide, and two antigen bindingsites. Each binding site comprises a heavy chain variable domain and alight chain variable domain with a total of 6 CDRs involved in antigenbinding per antigen binding site. Multispecific DVDs include DVD bindingproteins that bind DLL4 and VEGF, or C-met and EFGR or ErbB3 and EGFR.

Alkylating agents include altretamine, AMD-473, AP-5280, apaziquone,bendamustine, brostallicin, busulfan, carboquone, carmustine (BCNU),chlorambucil, CLORETAZINE® (laromustine, VNP 40101M), cyclophosphamide,decarbazine, estramustine, fotemustine, glufosfamide, ifosfamide,KW-2170, lomustine (CCNU), mafosfamide, melphalan, mitobronitol,mitolactol, nimustine, nitrogen mustard N-oxide, ranimustine,temozolomide, thiotepa, TREANDA® (bendamustine), treosulfan, rofosfamideand the like.

Angiogenesis inhibitors include endothelial-specific receptor tyrosinekinase (Tie-2) inhibitors, epidermal growth factor receptor (EGFR)inhibitors, insulin growth factor-2 receptor (IGFR-2) inhibitors, matrixmetalloproteinase-2 (MMP-2) inhibitors, matrix metalloproteinase-9(MMP-9) inhibitors, platelet-derived growth factor receptor (PDGFR)inhibitors, thrombospondin analogs, vascular endothelial growth factorreceptor tyrosine kinase (VEGFR) inhibitors and the like.

Antimetabolites include ALIMTA® (pemetrexed disodium, LY231514, MTA),5-azacitidine, XELODA® (capecitabine), carmofur, LEUSTAT® (cladribine),clofarabine, cytarabine, cytarabine ocfosfate, cytosine arabinoside,decitabine, deferoxamine, doxifluridine, eflornithine, EICAR(5-ethynyl-1-β-D-ribofuranosylimidazole-4-carboxamide), enocitabine,ethnylcytidine, fludarabine, 5-fluorouracil alone or in combination withleucovorin, GEMZAR® (gemcitabine), hydroxyurea, ALKERAN® (melphalan),mercaptopurine, 6-mercaptopurine riboside, methotrexate, mycophenolicacid, nelarabine, nolatrexed, ocfosfate, pelitrexol, pentostatin,raltitrexed, Ribavirin, triapine, trimetrexate, S-1, tiazofurin,tegafur, TS-1, vidarabine, UFT and the like.

Antivirals include ritonavir, hydroxychloroquine and the like.

Aurora kinase inhibitors include ABT-348, AZD-1152, MLN-8054, VX-680,Aurora A-specific kinase inhibitors, Aurora B-specific kinase inhibitorsand pan-Aurora kinase inhibitors and the like.

Bcl-2 protein inhibitors include AT-101 ((−)gossypol), GENASENSE® (G3139or oblimersen (Bcl-2-targeting antisense oligonucleotide)), IPI-194,IPI-565,N-(4-(4-((4′-chloro(1,1′-biphenyl)-2-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(dimethylamino)-1-((phenylsulfanyl)methyl)propyl)amino)-3-nitrobenzenesulfonamide)(ABT-737),N-(4-(4-((2-(4-chlorophenyl)-5,5-dimethyl-1-cyclohex-1-en-1-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzenesulfonamide(ABT-263), GX-070 (obatoclax) and the like.

Bcr-Abl kinase inhibitors include DASATINIB® (BMS-354825), GLEEVEC®(imatinib) and the like.

CDK inhibitors include AZD-5438, BMI-1040, BMS-032, BMS-387, CVT-2584,flavopyridol, GPC-286199, MCS-5A, PD0332991, PHA-690509, seliciclib(CYC-202, R-roscovitine), ZK-304709 and the like.

COX-2 inhibitors include ABT-963, ARCOXIA® (etoricoxib), BEXTRA®(valdecoxib), BMS347070, CELEBREX® (celecoxib), COX-189 (lumiracoxib),CT-3, DERAMAXX® (deracoxib), JTE-522,4-methyl-2-(3,4-dimethylphenyl)-1-(4-sulfamoylphenyl-1H-pyrrole), MK-663(etoricoxib), NS-398, parecoxib, RS-57067, SC-58125, SD-8381, SVT-2016,S-2474, T-614, VIOXX® (rofecoxib) and the like.

EGFR inhibitors include ABX-EGF, anti-EGFR immunoliposomes, EGF-vaccine,EMD-7200, ERBITUX® (cetuximab), HR3, IgA antibodies, IRESSA®(gefitinib), TARCEVA® (erlotinib or OSI-774), TP-38, EGFR fusionprotein, TYKERB® (lapatinib) and the like.

ErbB2 receptor inhibitors include CP-724-714, CI-1033 (canertinib),HERCEPTIN® (trastuzumab), TYKERB® (lapatinib), OMNITARG® (2C4,petuzumab), TAK-165, GW-572016 (ionafarnib), GW-282974, EKB-569, PI-166,dHER2 (HER2 vaccine), APC-8024 (HER-2 vaccine), anti-HER/2neu bispecificantibody, B7.her2IgG3, AS HER2 trifunctional bispecfic antibodies, mABAR-209, mAB 2B-1 and the like.

Histone deacetylase inhibitors include depsipeptide, LAQ-824, MS-275,trapoxin, suberoylanilide hydroxamic acid (SAHA), TSA, valproic acid andthe like.

HSP-90 inhibitors include 17-AAG-nab, 17-AAG, CNF-101, CNF-1010,CNF-2024, 17-DMAG, geldanamycin, IPI-504, KOS-953, MYCOGRAB® (humanrecombinant antibody to HSP-90), NCS-683664, PU24FC1, PU-3, radicicol,SNX-2112, STA-9090 VER49009 and the like.

Inhibitors of inhibitors of apoptosis proteins include HGS1029,GDC-0145, GDC-0152, LCL-161, LBW-242 and the like.

Antibody drug conjugates include anti-CD22-MC-MMAF, anti-CD22-MC-MMAE,anti-CD22-MCC-DM1, CR-011-veMMAE, PSMA-ADC, MEDI-547, SGN-19Am SGN-35,SGN-75 and the like

Activators of death receptor pathway include TRAIL, antibodies or otheragents that target TRAIL or death receptors (e.g., DR4 and DRS) such asApomab, conatumumab, ETR2-ST01, GDC0145, (lexatumumab), HGS-1029,LBY-135, PRO-1762 and trastuzumab.

Kinesin inhibitors include Eg5 inhibitors such as AZD4877, ARRY-520;CENPE inhibitors such as GSK923295A and the like.

JAK-2 inhibitors include CEP-701 (lesaurtinib), XL019 and INCB018424 andthe like.

MEK inhibitors include ARRY-142886, ARRY-438162 PD-325901, PD-98059 andthe like.

mTOR inhibitors include AP-23573, CCI-779, everolimus, RAD-001,rapamycin, temsirolimus, ATP-competitive TORC1/TORC2 inhibitors,including PI-103, PP242, PP30, Torin 1 and the like.

Non-steroidal anti-inflammatory drugs include AMIGESIC® (salsalate),DOLOBID® (diflunisal), MOTRIN® (ibuprofen), ORUDIS® (ketoprofen),RELAFEN® (nabumetone), FELDENE® (piroxicam), ibuprofen cream, ALEVE®(naproxen) and NAPROSYN® (naproxen), VOLTAREN® (diclofenac), INDOCIN®(indomethacin), CLINORIL® (sulindac), TOLECTIN® (tolmetin), LODINE®(etodolac), TORADOL® (ketorolac), DAYPRO® (oxaprozin) and the like.

PDGFR inhibitors include C-451, CP-673, CP-868596 and the like.

Platinum chemotherapeutics include cisplatin, ELOXATIN® (oxaliplatin)eptaplatin, lobaplatin, nedaplatin, PARAPLATIN® (carboplatin),satraplatin, picoplatin and the like.

Polo-like kinase inhibitors include BI-2536 and the like.

Phosphoinositide-3 kinase (PI3K) inhibitors include wortmannin,LY294002, XL-147, CAL-120, ONC-21, AEZS-127, ETP-45658, PX-866,GDC-0941, BGT226, BEZ235, XL765 and the like.

Thrombospondin analogs include ABT-510, ABT-567, ABT-898, TSP-1 and thelike.

VEGFR inhibitors include AVASTIN® (bevacizumab), ABT-869, AEE-788,ANGIOZYME™ (a ribozyme that inhibits angiogenesis (RibozymePharmaceuticals (Boulder, Colo.) and Chiron, (Emeryville, Calif.)),axitinib (AG-13736), AZD-2171, CP-547,632, IM-862, MACUGEN (pegaptamib),NEXAVAR® (sorafenib, BAY43-9006), pazopanib (GW-786034), vatalanib(PTK-787, ZK-222584), SUTENT® (sunitinib, SU-11248), VEGF trap, ZACTIMA™(vandetanib, ZD-6474), GA101, ofatumumab, ABT-806 (mAb-806), ErbB3specific antibodies, BSG2 specific antibodies, DLL4 specific antibodiesand C-met specific antibodies, and the like.

Antibiotics include intercalating antibiotics aclarubicin, actinomycinD, amrubicin, annamycin, adriamycin, BLENOXANE® (bleomycin),daunorubicin, CAELYX® or MYOCET® (liposomal doxorubicin), elsamitrucin,epirbucin, glarbuicin, ZAVEDOS® (idarubicin), mitomycin C, nemorubicin,neocarzinostatin, peplomycin, pirarubicin, rebeccamycin, stimalamer,streptozocin, VALSTAR® (valrubicin), zinostatin and the like.

Topoisomerase inhibitors include aclarubicin, 9-aminocamptothecin,amonafide, amsacrine, becatecarin, belotecan, BN-80915, CAMPTOSAR®(irinotecan hydrochloride), camptothecin, CARDIOXANE® (dexrazoxine),diflomotecan, edotecarin, ELLENCE® or PHARMORUBICIN® (epirubicin),etoposide, exatecan, 10-hydroxycamptothecin, gimatecan, lurtotecan,mitoxantrone, orathecin, pirarbucin, pixantrone, rubitecan, sobuzoxane,SN-38, tafluposide, topotecan and the like.

Antibodies include AVASTIN® (bevacizumab), CD40-specific antibodies,chTNT-1/B, denosumab, ERBITUX® (cetuximab), HUMAX-CD4® (zanolimumab),IGF1R-specific antibodies, lintuzumab, PANOREX® (edrecolomab), RENCAREX®(WX G250), RITUXAN® (rituximab), ticilimumab, trastuzimab, CD20antibodies types I and II and the like.

Hormonal therapies include ARIMIDEX® (anastrozole), AROMASIN®(exemestane), arzoxifene, CASODEX® (bicalutamide), CETROTIDE®(cetrorelix), degarelix, deslorelin, DESOPAN® (trilostane),dexamethasone, DROGENIL® (flutamide), EVISTA® (raloxifene),

AFEMATM (fadrozole), FARESTON® (toremifene), FASLODEX® (fulvestrant),FEMARA® (letrozole), formestane, glucocorticoids, HECTOROL®(doxercalciferol), RENAGEL® (sevelamer carbonate), lasofoxifene,leuprolide acetate, MEGACE® (megesterol), MIFEPREX® (mifepristone),NILANDRON™ (nilutamide), NOLVADEX® (tamoxifen citrate), PLENAXIS™(abarelix), prednisone, PROPECIA® (finasteride), rilostane, SUPREFACT®(buserelin), TRELSTAR® (luteinizing hormone releasing hormone (LHRH)),VANTAS® (Histrelin implant), VETORYL® (trilostane or modrastane),ZOLADEX® (fosrelin, goserelin) and the like.

Deltoids and retinoids include seocalcitol (EB1089, CB1093),lexacalcitrol (KH1060), fenretinide, PANRETIN® (aliretinoin), ATRAGEN®(liposomal tretinoin), TARGRETIN® (bexarotene), LGD-1550 and the like.

PARP inhibitors include ABT-888 (veliparib), olaparib, KU-59436,AZD-2281, AG-014699, BSI-201, BGP-15, INO-1001, ONO-2231 and the like.

Plant alkaloids include, but are not limited to, vincristine,vinblastine, vindesine, vinorelbine and the like.

Proteasome inhibitors include VELCADE® (bortezomib), MG132, NPI-0052,PR-171 and the like.

Examples of immunologicals include interferons and otherimmune-enhancing agents. Interferons include interferon alpha,interferon alpha-2a, interferon alpha-2b, interferon beta, interferongamma-1a, ACTIMMUNE® (interferon gamma-1b) or interferon gamma-n1,combinations thereof and the like. Other agents include ALFAFERONE®,(IFN-α), BAM-002 (oxidized glutathione), BEROMUN® (tasonermin), BEXXAR®(tositumomab), CAMPATH® (alemtuzumab), CTLA4 (cytotoxic lymphocyteantigen 4), decarbazine, denileukin, epratuzumab, GRANOCYTE®(lenograstim), lentinan, leukocyte alpha interferon, imiquimod, MDX-010(anti-CTLA-4), melanoma vaccine, mitumomab, molgramostim, MYLOTARG™(gemtuzumab ozogamicin), NEUPOGEN® (filgrastim), OncoVAC-CL, OVAREX®(oregovomab), pemtumomab (Y-muHMFG1), PROVENGE® (sipuleucel-T),sargaramostim, sizofilan, teceleukin, THERACYS® (BacillusCalmette-Guerin), ubenimex, VIRULIZIN° (immunotherapeutic, LorusPharmaceuticals), Z-100 (Specific Substance of Maruyama (SSM)), WF-10(Tetrachlorodecaoxide (TCDO)), PROLEUKIN® (aldesleukin), ZADAXIN®(thymalfasin), ZENAPAX® (daclizumab), ZEVALIN® (90Y-Ibritumomabtiuxetan) and the like.

Biological response modifiers are agents that modify defense mechanismsof living organisms or biological responses, such as survival, growth ordifferentiation of tissue cells to direct them to have anti-tumoractivity and include krestin, lentinan, sizofiran, picibanil PF-3512676(CpG-8954), ubenimex and the like.

Pyrimidine analogs include cytarabine (ara C or Arabinoside C), cytosinearabinoside, doxifluridine, FLUDARA® (fludarabine), 5-FU(5-fluorouracil), floxuridine, GEMZAR® (gemcitabine), TOMUDEX®(ratitrexed), TROXATYL™ (triacetyluridine troxacitabine) and the like.

Purine analogs include LANVIS® (thioguanine) and PURI-NETHOL®(mercaptopurine).

Antimitotic agents include batabulin, epothilone D (KOS-862),N-(2-((4-hydroxyphenyl)amino)pyridin-3-yl)-4-methoxybenzenesulfonamide,ixabepilone (BMS 247550), paclitaxel, TAXOTERE® (docetaxel), PNU100940(109881), patupilone, XRP-9881 (larotaxel), vinflunine, ZK-EPO(synthetic epothilone) and the like.

Ubiquitin ligase inhibitors include MDM2 inhibitors, such as nutlins,NEDD8 inhibitors such as MLN4924 and the like.

Compounds of this invention can also be used as radiosensitizers thatenhance the efficacy of radiotherapy. Examples of radiotherapy includeexternal beam radiotherapy, teletherapy, brachytherapy and sealed,unsealed source radiotherapy and the like.

Additionally, compounds having Formula (I) may be combined with otherchemotherapeutic agents such as ABRAXANE™ (ABI-007), ABT-100 (farnesyltransferase inhibitor), ADVEXIN® (Ad5CMV-p53 vaccine), ALTOCOR® orMEVACOR® (lovastatin), AMPLIGEN® (poly I:poly C12U, a synthetic RNA),APTOSYN® (exisulind), AREDIA® (pamidronic acid), arglabin,L-asparaginase, atamestane (1-methyl-3,17-dione-androsta-1,4-diene),AVAGE® (tazarotene), AVE-8062 (combreastatin derivative) BEC2(mitumomab), cachectin or cachexin (tumor necrosis factor), canvaxin(vaccine), CEAVAC® (cancer vaccine), CELEUK® (celmoleukin), CEPLENE®(histamine dihydrochloride), CERVARIX® (human papillomavirus vaccine),CHOP® (C: CYTOXAN® (cyclophosphamide); H: ADRIAMYCIN®(hydroxydoxorubicin); O: Vincristine (ONCOVIN®); P: prednisone), CYPAT™(cyproterone acetate), combrestatin A4P, DAB(389)EGF (catalytic andtranslocation domains of diphtheria toxin fused via a His-Ala linker tohuman epidermal growth factor) or TransMID-107R™ (diphtheria toxins),dacarbazine, dactinomycin, 5,6-dimethylxanthenone-4-acetic acid (DMXAA),eniluracil, EVIZON™ (squalamine lactate), DIMERICINE® (T4N5 liposomelotion), discodermolide, DX-8951f (exatecan mesylate), enzastaurin,EPO906 (epithilone B), GARDASIL® (quadrivalent human papillomavirus(Types 6, 11, 16, 18) recombinant vaccine), GASTRIMMUNE®, GENASENSE®,GMK (ganglioside conjugate vaccine), GVAX® (prostate cancer vaccine),halofuginone, histerelin, hydroxycarbamide, ibandronic acid, IGN-101,IL-13-PE38, IL-13-PE38QQR (cintredekin besudotox), IL-13-pseudomonasexotoxin, interferon-α, interferon-γ, JUNOVAN™ or MEPACT™ (mifamurtide),lonafarnib, 5,10-methylenetetrahydrofolate, miltefosine(hexadecylphosphocholine), NEOVASTAT® (AE-941), NEUTREXIN® (trimetrexateglucuronate), NIPENT® (pentostatin), ONCONASE® (a ribonuclease enzyme),ONCOPHAGE® (melanoma vaccine treatment), ONCOVAX® (IL-2 Vaccine),ORATHECIN™ (rubitecan), OSIDEM® (antibody-based cell drug), OVAREX® MAb(murine monoclonal antibody), paclitaxel, PANDIMEX™ (aglycone saponinsfrom ginseng comprising 20(S)protopanaxadiol (aPPD) and20(S)protopanaxatriol (aPPT)), panitumumab, PANVAC®-VF (investigationalcancer vaccine), pegaspargase, PEG Interferon A, phenoxodiol,procarbazine, rebimastat, REMOVAB® (catumaxomab), REVLIMID®(lenalidomide), RSR13 (efaproxiral), SOMATULINE® LA (lanreotide),SORIATANE® (acitretin), staurosporine (Streptomyces staurospores),talabostat (PT100), TARGRETIN® (bexarotene), TAXOPREXIN®(DHA-paclitaxel), TELCYTA® (canfosfamide, TLK286), temilifene, TEMODAR®(temozolomide), tesmilifene, thalidomide, THERATOPE® (STn-KLH), thymitaq(2-amino-3,4-dihydro-6-methyl-4-oxo-5-(4-pyridylthio)quinazolinedihydrochloride), TNFERADE™ (adenovector: DNA carrier containing thegene for tumor necrosis factor-α), TRACLEER® or ZAVESCA® (bosentan),tretinoin (Retin-A), tetrandrine, TRISENOX® (arsenic trioxide),VIRULIZIN®, ukrain (derivative of alkaloids from the greater celandineplant), vitaxin (anti-alphavbeta3 antibody), XCYTRIN® (motexafingadolinium), XINLAY™ (atrasentan), XYOTAX™ (paclitaxel poliglumex),YONDELIS® (trabectedin), ZD-6126, ZINECARD® (dexrazoxane), ZOMETA®(zolendronic acid), zorubicin and the like.

The following examples are presented to provide what is believed to bethe most useful and readily understood description of procedures andconceptual aspects of this invention. The exemplified compounds werenamed using ACD/ChemSketch, Release 12.00 Version 12.01 (13 May 2009,Advanced Chemistry Development Inc.,Toronto, Ontario), or ChemDraw® Ver.9.0.5 (CambridgeSoft, Cambridge, Mass.). Intermediates were named usingChemDraw® Ver. 9.0.5 (CambridgeSoft, Cambridge, Mass.).

EXAMPLES Example 12-(cyclohexylamino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-oneExample 1A3-(6-methoxy-2-(methylthio)pyrimidin-4-yl)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine

A mixture of 4-chloro-6-methoxy-2-(methylthio)pyrimidine (10.2 g, 53 7mmol),1-(phenylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine(18.8 g, 48.8 mmol), potassium carbonate (48.8 g, 98 mmol), andtetrakis(triphenylphosphine) palladium (2.26 g, 1.95 mmol) in 9/1dimethoxyethane/N,N-dimethylformamide (200 mL) was evacuated undervacuum and refilled with nitrogen and heated at 85° C. for 20 minutes.The cooled mixture was filtered to give the title compound.

Example 1B3-(6-methoxy-2-(methylsulfonyl)pyrimidin-4-yl)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine

A mixture of EXAMPLE 1A (6.2 g, 15 0 mmol) and OXONE® (92 g, 150 mmol)in ethyl acetate (350 mL) was stirred at 77° C. for 2 days. The mixturewas filtered and the solids were washed with dichloromethane andconcentrated to give the title compound.

Example 1CN-cyclohexyl-4-methoxy-6-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-amine

A solution of EXAMPLE 1B (6.7 g, 15.1 mmol) and cyclohexanamine (6.90mL, 60.3 mmol) in dioxane (165 mL) was heated at 100° C. overnight. Themixture was concentrated to afford the crude title compound which wasdirectly used in the next step.

Example 1D2-(cyclohexylamino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-onehydrochloride

To EXAMPLE 1C (6.99 g, ˜15.1 mmol) was added dioxane (150 mL) andaqueous 1M NaOH (75 mL, 75 mmol). The mixture was heated at 100° C. for1.5 hours and concentrated. The residue was partitioned between waterand dichloromethane and the organic layer dried over sodium sulfate,filtered through silica gel with ethyl acetate, and concentrated. Theresidue was dissolved in 12% aqueous HCl (55 mL, 199 mmol) and heated at80° C. for 2 days. The cooled mixture was filtered, and the crude HClsalt was isolated.

Example 1E2-(cyclohexylamino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The HCl salt from EXAMPLE 1D was dissolved in methanol (500 mL) and 7Mammonia in methanol (13.9 mL, 97 mmol) was added dropwise. The mixturewas stirred at room temperature for 10 minutes and concentrated. Theresidue was washed with water and concentrated to provide the titlecompound as the free base. MS (ESI) m/e 310 (M+H)⁺; ¹H NMR (DMSO-d₆) δ1.17-1.81 (m, 8H), 1.93-2.07 (m, 2H), 3.71-3.98 (m, 1H), 6.05 (s, 1H),6.37 (d, J=6.35 Hz, 1H), 7.15 (dd, J=8.13, 4.56 Hz, 1H), 8.19 (d, J=2.78Hz, 1H), 8.25 (dd, J=4.76, 1.59 Hz, 1H), 8.63 (d, J=7.14 Hz, 1H), 10.17(s, 1H), 12.11 (s, 1H).

Example 22-(benzylamino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the free base using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine with benzylamine MS(ESI) m/e 318 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 4.65 (d, J=5.83 Hz, 2H), 6.08(s, 1H), 6.92 (s, 1H), 7.06 (dd, J=7.98, 4.91 Hz, 1H), 7.26 (t, J=7.21Hz, 1H), 7.32-7.47 (m, 4H), 8.16 (d, J=1.53 Hz, 1H), 8.22 (dd, J=4.60,1.84 Hz, 1H), 8.38-8.50 (m, 1H), 10.57 (s, 1H), 12.07 (s, 1H).

Example 3 2-anilino-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

A mixture of EXAMPLE 1B (0.089 g, 0.20 mmol), and aniline (0.2 mL) inN-methylpyrrolidone (3 mL) was heated in a microwave at 235° C. for 1.5hours. The mixture was concentrated and purified by reverse phase HPLCto provide the title compound. MS (ESI) m/e 304 (M+H)⁺; ¹H NMR (DMSO-d₆)δ 6.33 (s, 1H), 7.06-7.18 (m, 2H), 7.34-7.45 (m, 2H), 7.68 (d, J=7.67Hz, 2H), 8.23 (s, 1H), 8.26-8.31 (m, 1H), 8.56 (d, J=7.67 Hz, 1H), 8.84(s, 1H), 12.22 (s, 1H).

Example 42-[(trans-4-aminocyclohexyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine withtrans-1,4-diaminocyclohexane. MS (ESI) m/e 325 (M+H)⁺; ¹H NMR (DMSO-d₆)δ 1.29-1.48 (m, 2H), 1.50-1.65 (m, 2H), 2.05 (t, J=14.49 Hz, 4H), 3.08(d, J=4.27 Hz, 1H), 3.84 (s, 1H), 6.46 (s, 1H), 7.34 (s, 1H), 8.26 (d,J=4.27 Hz, 3H), 8.36-8.45 (m, 1H), 8.45-8.56 (m, 1H), 8.76 (s, 1H), 9.23(s, 1H), 12.91 (s, 1H).

Example 52-[(3,5-difluorobenzyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine with(3,5-difluorophenyl)methanamine MS (ESI) m/e 354 (M+H)⁺; ¹H NMR(DMSO-d₆) δ 4.72 (d, J=3.38 Hz, 2H), 6.40 (s, 1H), 6.94-7.43 (m, 5H),8.20-8.73 (m, 4H), 12.70 (s, 1H).

Example 62-(piperidin-4-ylamino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine with piperidin-4-amineMS (ESI) m/e 311 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 1.29-1.43 (m, 2H), 1.81-1.92(m, 5H), 2.98-3.12 (m, 3H), 4.44 (d, J=13.20 Hz, 2H), 6.16 (s, 1H), 7.18(dd, J=7.83, 4.76 Hz, 1H), 8.22 (s, 1H), 8.26 (dd, J=4.60, 1.53Hz, 1H),8.55 (dd, J=7.98, 1.23Hz, 1H).

Example 72-(4-hydroxypiperidin-1-yl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine with piperidin-4-ol.MS (ESI) m/e 312 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 1.38-1.57 (m, 2H), 1.76-1.96(m, 2H), 3.37-3.55 (m, 2H), 3.75-3.88 (m, 1H), 4.07-4.21 (m, 2H), 6.38(s, 1H), 7.44 (dd, J=7.98, 5.22 Hz, 1H), 8.39-8.47 (m, 1H), 8.74 (d,J=7.67 Hz, 1H), 12.99 (s, 1H).

Example 82-{[(1S)-1-phenylethyl]amino}-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine with(S)-1-phenylethanamine. MS (ESI) m/e 332 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 1.51(d, J=6.75Hz, 3H), 5.19 (q, J=6.85Hz, 1H), 6.04 (s, 1H), 6.92 (s, 1H),7.07 (dd, J=7.98, 4.60 Hz, 1H), 7.24 (t, J=7.36 Hz, 1H), 7.33-7.48 (m,4H), 8.11 (s, 1H), 8.22 (dd, J=4.60, 1.53Hz, 1H), 8.34 (d, J=7.67 Hz,1H), 10.27 (s, 1H), 12.04 (s, 1H).

Example 96-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(tetrahydro-2H-pyran-4-ylamino)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine withtetrahydro-2H-pyran-4-amine MS (ESI) m/e 332 (M+H)⁺; ¹H NMR (DMSO-d₆) δ1.37-1.67 (m, 2H), 1.96 (d, J=10.68 Hz, 2H), 3.45 (t, J=10.22 Hz, 2H),3.85-3.96 (m, 2H), 4.05-4.18 (m, 2H), 6.46 (s, 1H), 7.28-7.38 (m, 1H),8.35-8.47 (m, 1H), 8.46-8.59 (m, 1H), 8.75 (s, 1H), 9.37 (d, J=5.49 Hz,1H), 12.90 (s, 1H).

Example 106-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[(tetrahydrofuran-2-ylmethyl)amino]pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine with(tetrahydrofuran-2-yl)methanamine MS (ESI) m/e 325 (M+H)⁺; ¹H NMR(DMSO-d₆) δ 1.54-1.70 (m, 1H), 1.77-2.09 (m, 3H), 3.48-3.74 (m, 3H),3.81-3.90 (m, 1H), 3.98-4.10 (m, 1H), 6.49 (s, 1H), 7.29-7.39 (m, 1H),8.42 (dd, J=4.88, 1.22 Hz, 1H), 8.50 (s, 1H), 8.84 (s, 1H), 9.02 (s,1H), 12.92 (s, 1H).

Example 112-[cyclohexyl(methyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine withN-methylcyclohexanamine MS (ESI) m/e 324 (M+H)⁺; ¹H NMR (DMSO-d₆) δ1.07-1.25 (m, 1H), 1.34-1.76 (m, 7H), 1.83 (d, J=12.58 Hz, 2H), 2.98 (s,3H), 4.51 (t, J=11.35Hz, 1H), 6.10 (s, 1H), 7.17 (dd, J=7.98, 4.60 Hz,1H), 8.20 (d, J=2.15 Hz, 1H), 8.26 (dd, J=4.60, 1.23 Hz, 1H), 8.57-8.68(m, 1H), 10.70 (s, 1H), 12.08 (s, 1H).

Example 122-{[(1R)-1-phenylethyl]amino}-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine with(R)-1-phenylethanamine MS (ESI) m/e 332 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 1.51(d, J=6.75Hz, 3H), 5.19 (q, J=7.06Hz, 1H), 6.04 (s, 1H), 6.92 (s, 1H),7.07 (dd, J=7.98, 4.60 Hz, 1H), 7.24 (t, J=7.36Hz, 1H), 7.37 (t, J=7.67Hz, 2H), 7.41-7.47 (m, 2H), 8.10 (s, 1H), 8.22 (dd, J=4.60, 1.53 Hz,1H), 8.34 (d, J=7.67 Hz, 1H), 10.26 (s, 1H), 12.03 (s, 1H).

Example 132-[(2-aminocyclohexyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine withcyclohexane-1,2-diamine MS (ESI) m/e 325 (M+H)⁺; ¹H NMR (DMSO-d₆) δ1.19-2.19 (m, 10H), 3.02-3.19 (m, 1H), 4.07 (s, 1H), 7.19-7.49 (m, 2H),8.14-8.65 (m, 5H), 12.96 (s, 1H).

Example 142-(cycloheptylamino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine with cycloheptanamineMS (ESI) m/e 324 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 1.44-1.74 (m, 10 H),1.91-2.08 (m, 2H), 3.95-4.15 (m, 1H), 6.06 (s, 1H), 6.37 (s, 1H), 7.15(dd, J=7.97, 4.58 Hz, 1H), 8.19 (d, J=2.37 Hz, 1H), 8.25 (dd, J=4.75,1.69 Hz, 1H), 8.64 (d, J=8.14 Hz, 1H), 10.17 (s, 1H), 12.13 (s, 1H).

Example 156-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(thiomorpholin-4-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine with thiomorpholine.MS (ESI) m/e 314 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 2.61-2.75 (m, 4H), 3.99-4.14(m, 4H), 6.21 (s, 1H), 7.18 (dd, J=7.93, 4.88 Hz, 1H), 8.21-8.31 (m,2H), 8.53 (d, J=7.32 Hz, 1H), 10.99 (s, 1H), 12.16 (s, 1H).

Example 162-{[2-(methylamino)ethyl]amino}-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine withN¹-methylethane-1,2-diamine. MS (ESI) m/e 285 (M+H)⁺; ¹H NMR (DMSO-d₆) δ2.35 (s, 3H), 2.70-2.80 (m, 2H), 3.43-3.54 (m, 3H), 6.05 (s, 1H), 6.60(s, 1H), 7.15 (dd, J=7.97, 4.58 Hz, 1H), 8.18 (s, 1H), 8.25 (dd, J=4.58,1.53 Hz, 1H), 8.62 (dd, J=8.14, 1.70 Hz, 1H).

Example 172-[bis(2-methoxyethyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine withbis(2-methoxyethyl)amine MS (ESI) m/e 344 (M+H)⁺; ¹H NMR (DMSO-d₆) δ3.30 (s, 6H), 3.61 (t, J=5.06Hz, 4H), 3.76-3.95 (m, 4H), 6.36 (s, 1H),7.34-7.43 (m, 1H), 8.38-8.44 (m, 1H), 8.36 (s, 1H), 8.81 (d, J=7.36 Hz,1H), 12.85 (s, 1H).

Example 182-[(2-methoxyethyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine with2-methoxyethanamine MS (ESI) m/e 286 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 3.32 (s,3H), 3.52-3.65 (m, 4H), 6.08 (s, 1H), 6.47-6.58 (m, 1H), 7.16 (dd,J=7.93, 4.88 Hz, 1H), 8.20 (d, J=1.22 Hz, 1H), 8.26 (dd, J=4.58, 1.53Hz, 1H), 8.61 (d, J=7.02 Hz, 1H), 10.47 (s, 1H), 12.13 (s, 1H).

Example 192-[(2-hydroxyethyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine with 2-aminoethanol.MS (ESI) m/e 272 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 3.50 (q, J=5.42 Hz, 2H),3.62 (t, J=5.52 Hz, 2H), 6.05 (s, 1H), 6.61 (s, 1H), 7.16 (dd, J=7.98,4.60 Hz, 1H), 8.17 (s, 1H), 8.25 (dd, J=4.60, 1.53 Hz, 1H), 8.60 (dd,J=7.98, 1.53 Hz, 1H).

Example 206-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-{[2-(trifluoromethyl)benzyl]amino}pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine with(2-(trifluoromethyl)phenyl)methanamine MS (ESI) m/e 386 (M+H)⁺; ¹H NMR(DMSO-d₆) δ 4.89 (d, J=4.30 Hz, 2H), 6.48 (s, 1H), 7.23 (s, 1H),7.46-7.59 (m, 1H), 7.70 (d, J=3.99 Hz, 2H), 7.80 (d, J=7.67 Hz, 1H),8.27-8.93 (m, 3H), 12.81 (s, 1H).

Example 212-[4-(hydroxymethyl)piperidin-1-yl]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine withpiperidin-4-ylmethanol. MS (ESI) m/e 326 (M+H)⁺; ¹H NMR (DMSO-d₆) δ1.05-1.35 (m, 2H), 1.59-1.88 (m, 3H), 3.03 (t, J=12.04 Hz, 2H), 3.30 (d,J=5.76 Hz, 2H), 4.51 (d, J=12.89 Hz, 2H), 6.29 (s, 1H), 7.36 (dd,J=8.14, 5.09 Hz, 1H), 8.30-8.45 (m, 2H), 8.67 (d, J=7.80 Hz, 1H), 12.73(s, 1H).

Example 222-{[3-(morpholin-4-yl)propyl]amino}-6-(1H-pynolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine with3-morpholinopropan-1-amine MS (ESI) m/e 355 (M+H)⁺; ¹H NMR (DMSO-d₆) δ1.66-1.83 (m, 2H), 2.25-2.43 (m, 6H), 3.45 (q, J=6.44 Hz, 2H), 3.52-3.65(m, 5H), 6.04 (s, 1H), 6.74 (s, 1H), 7.15 (dd, J=7.98, 4.60 Hz, 1H),8.16 (s, 1H), 8.23-8.29 (m, 1H), 8.58-8.68 (m, 1H).

Example 232-[(3-hydroxybenzyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine with3-(aminomethyl)phenol. MS (ESI) m/e 334 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 4.63(d, J=3.68 Hz, 2H), 6.48 (s, 1H), 6.66-6.74 (m, 1H), 6.78-6.87 (m, 2H),7.17 (t, J=7.83 Hz, 1H), 7.32 (dd, J=7.98, 4.91 Hz, 1H), 8.41 (d, J=3.68Hz, 1H), 8.52 (d, J=7.06 Hz, 1H), 8.73 (s, 1H), 9.22 (s, 1H), 12.86 (s,1H).

Example 242-(morpholin-4-yl)-6-(1H-pynolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine with morpholine. MS(ESI) m/e 298 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 3.56-3.83 (m, 8H), 6.22 (s,1H), 7.18 (dd, J=7.98, 4.60 Hz, 1H), 8.16-8.37 (m, 2H), 8.55 (d, J=7.98Hz, 1H), 10.95 (s, 1H), 12.12 (s, 1H).

Example 251-[6-oxo-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,6-dihydropyrimidin-2-yl]piperidine-4-carboxylicacid

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine withpiperidine-4-carboxamide. MS (ESI) m/e 340 (M+H)⁺; ¹H NMR (DMSO-d₆) δ1.54-1.73 (m, 2H), 1.90-2.00 (m, 2H), 2.56-2.69 (m, 1H), 3.16-3.31 (m,2H), 4.39 (d, J=13.50 Hz, 2H), 6.37 (s, 1H), 7.43 (dd, J=7.98, 5.22 Hz,1H), 8.38-8.48 (m, 2H), 8.76 (d, J=7.67 Hz, 1H), 12.94 (s, 1H).

Example 262-(cyclopentylamino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine with cyclopentanamineMS (ESI) m/e 295 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 1.45-1.79 (m, 6H), 1.91-2.13(m, 2H), 4.21-4.39 (m, 1H), 6.06 (s, 1H), 6.40-6.51 (m, 1H), 7.16 (dd,J=7.98, 4.60 Hz, 1H), 8.18 (d, J=1.84 Hz, 1H), 8.25 (dd, J=4.60, 1.53Hz, 1H), 8.64 (dd, J=7.98, 1.23 Hz, 1H), 10.13 (s, 1H), 12.09 (s, 1H).

Example 272-(4-methoxypiperidin-1-yl)-6-(1H-pynolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine with4-methoxypiperidine. MS (ESI) m/e 326 (M+H)⁺; ¹H NMR (DMSO-d₆) δ1.46-1.60 (m, 2H), 1.88-2.00 (m, 2H), 3.30 (s, 3H), 3.42-3.57 (m, 3H),4.00-4.14 (m, 2H), 6.34 (s, 1H), 7.40 (dd, J=7.21, 5.06 Hz, 1H), 8.40(s, 2H), 8.73 (d, J=7.67 Hz, 1H), 12.85 (s, 1H).

Example 282-[(2-hydroxycyclohexyl)amino]-6-(1H-pynolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine with2-aminocyclohexanol. MS (ESI) m/e 326 (M+H)⁺; ¹H NMR (DMSO-d₆) δ1.13-1.79 (m, 8H), 2.98-3.09 (m, 1H), 3.86-3.93 (m, 1H), 5.88 (s, 1H),7.29 (dd, J=7.93, 4.88 Hz, 1H), 7.81-7.95 (m, 2H), 8.31-8.40 (m, 2H),10.97 (d, J=30.82 Hz, 1H), 12.65 (s, 1H).

Example 292-[(1-methylpiperidin-4-yl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine with1-methylpiperidin-4-amine MS (ESI) m/e 325 (M+H)⁺; ¹H NMR (DMSO-d₆) δ1.47-1.60 (m, 2H), 1.93-2.02 (m, 2H), 2.06-2.16 (m, 2H), 2.21 (s, 3H),2.68-2.79 (m, 2H), 3.78-3.92 (m, 1H), 6.04 (s, 1H), 6.88-7.01 (m, 1H),7.15 (dd, J=7.98, 4.60 Hz, 1H), 8.17 (s, 1H), 8.23-8.27 (m, 1H), 8.61(dd, J=7.98, 1.53 Hz, 1H).

Example 302-{[3-(1H-imidazol-1-yl)propyl]amino}-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine with3-(1H-imidazol-1-yl)propan-1-amine MS (ESI) m/e 336 (M+H)⁺; ¹H NMR(DMSO-d₆) δ 2.00-2.10 (m, 2H), 3.17 (s, 1H), 3.33-3.40 (m, 2H),3.51-3.59 (m, 1H), 4.09 (t, J=6.90 Hz, 2H), 6.06 (s, 1H), 6.78-6.86 (m,1H), 6.92 (s, 1H), 7.17 (dd, J=7.98, 4.60 Hz, 1H), 7.22 (s, 1H), 7.67(s, 1H), 8.15 (s, 1H), 8.25 (dd, J=4.60, 1.53 Hz, 1H), 8.52 (dd, J=7.98,1.53 Hz, 1H).

Example 312-({2-[2-(2-aminoethoxy)ethoxy]ethyl}amino)-6-(1H-pynolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared as the HCl salt using the proceduredescribed for EXAMPLE 1 replacing cyclohexanamine with2,2′-(ethane-1,2-diylbis(oxy))diethanamine MS (ESI) m/e 359 (M+H)⁺; ¹HNMR (DMSO-d₆) δ 2.74 (t, J=5.59 Hz, 2H), 3.45 (t, J=5.76 Hz, 2H),3.51-3.69 (m, 8H), 6.04 (s, 1H), 7.00-7.11 (m, 1H), 7.15 (dd, J=7.97,4.58 Hz, 1H), 8.18 (s, 1H), 8.25 (dd, J=4.75, 1.70 Hz, 1H), 8.60 (dd,J=8.14, 1.70 Hz, 1H).

Example 32 2-phenyl-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

To a solution of EXAMPLE 1B (89 mg, 0.20 mmol) in 1,2-dimethoxyethane (2mL) at 0° C. was added dropwise 3M phenylmagnesium bromide in diethylether (0.133 mL, 0.40 mmol)). The mixture was slowly warmed to roomtemperature and stirred for 15 minutes. To the solution was addeddropwise 1M aqueous sodium hydroxide (2 mL, 2 mmol). The mixture wasstirred at room temperature for 1 day and concentrated. The residue wasdissolved in 12% aqueous HCl (0.62 mL, 2.25 mmol) and heated at 90° C.for 4 hours. The mixture was concentrated and purified by reverse phaseHPLC to provide the title compound. MS (ESI) m/e 289 (M+H)⁺; ¹H NMR(DMSO-d₆) δ 6.78 (s, 1H), 7.25 (dd, J=7.93, 4.58 Hz, 1H), 7.54-7.65 (m,3H), 8.24-8.34 (m, 3H), 8.44 (s, 1H), 8.69-8.75 (m, 1H), 12.32 (s, 1H).

Example 332-(2-methylphenyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared using the procedure described forEXAMPLE 32 replacing phenylmagnesium bromide with o-tolylmagnesiumbromide. MS (ESI) m/e 303 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 2.45 (s, 3H), 6.74(s, 1H), 7.17 (dd, J=7.93, 4.58 Hz, 1H), 7.31-7.41 (m, 2H), 7.45 (t,J=7.48 Hz, 1H), 7.55 (d, J=7.63 Hz, 1H), 8.28 (dd, J=4.58, 1.53 Hz, 1H),8.32 (s, 1H), 8.55 (d, J=7.3 2 Hz, 1H), 12.28 (s, 1H), 12.42 (s, 1H).

Example 34 6-phenyl-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-oneExample 34A 2-tert-butoxy-6-chloro-4-iodopyridine

To a solution of 2,6 dichloro-4-iodo pyridine (1 g, 3.65 mmol) in 15 mLtetrahydrofuran was added 1M potassium tert-butoxide (4.02 mL, 4.02mmol) and the solution heated at reflux for 2 hours. The mixture wasdiluted with ethyl acetate, washed with water and brine and dried overmagnesium sulfate, filtered and concentrated. The crude material wasused without further purification. MS (DCI) m/e 312.0 (M+H)⁺.

Example 34B3-(2-tert-butoxy-6-chloropyridin-4-yl)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine

To a solution of EXAMPLE 34A (2.6 g, 8.35 mmol) in 5:1dimethoxyethane/ethanol (90 mL) was added1-(phenylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine(3.53 g, 9.18 mmol), 1M aqueous sodium carbonate (6.68 mL) anddichlorobis (triphenylphosphine)-palladium (II) (0.29 g, 0.42 mmol). Thereaction was heated at 80° C. for 3 hours, cooled, and diluted withethyl acetate. The solution was washed with brine, dried over magnesiumsulfate, filtered and concentrated to give the title compound. MS (ESI)m/e 442.0 (M+H)⁺.

Example 34C3-(2-tert-butoxy-6-chloropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

To a suspension of EXAMPLE 34B (2.15 g, 4.87 mmol) in 60 mLethanol/water (5:1) was added powdered potassium hydroxide (1.09 g,19.46 mmol). The suspension was heated at 50° C. for 3 hours, at whichtime the reaction was homogeneous. The solvent was removed and the crudematerial was dissolved in ethyl acetate, washed with water, and brine,dried over magnesium sulfate, filtered and concentrated. The crudematerial was purified by flash chromatography (Analogix 280, gradientelution, 20-100% ethyl acetate/hexane) to give the title compound. MS(ESI) m/e 301.9 (M+H)⁺.

Example 34D3-(2-tert-butoxy-6-phenylpyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

To a solution of EXAMPLE 34C (0.13 g, 0.43 mmol) in 7:3:2dimethoxyethane/ethanol/water (3 mL) was added phenyl boronic acid(0.053 g, 0.43 mmol), 1M aqueous sodium carbonate (0.6 mL) anddichlorobis (triphenylphosphine)-palladium (II) (0.015 g, 0.022 mmol).The solution was heated to 160° C. in a CEM microwave @100 W for 20minutes. The crude material was diluted with ethyl acetate, washed withbrine, dried over magnesium sulfate, filtered, and concentrated.Purification by flash chromatography (Analogix 280, gradient elution,5-75% ethyl acetate/hexane) gave the title compound. MS (ESI) m/e 344.0(M+H)⁺.

Example 34E 6-phenyl-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one

To a solution of EXAMPLE 34D in 1 mL dichloromethane was added 1 mLtrifluoroacetic acid. The solution was stirred at room temperature for25 minutes and the solvent was removed. The crude material was dilutedwith ethyl acetate and washed with saturated sodium bicarbonate andbrine, dried over magnesium sulfate, filtered, and concentrated to givethe title compound. MS (ESI) m/e 287.9 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 6.70(s, 1H), 7.03 (s, 1H), 7.11-7.30 (m, 1H), 7.37-7.64 (m, 3H), 7.76-8.01(m, 2H), 8.18-8.48 (m, 3H), 11.52 (s, 1H), 12.23 (s, 1H).

Example 354-(1H-pyrrolo[2,3-b]pyridin-3-yl)-6-[3-(trifluoromethoxy)phenyl]pyridin-2(1H)-oneExample 35A3-(2-tert-butoxy-6-(3-(trifluoromethoxy)phenyl)pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

The title compound was prepared using the procedure described forEXAMPLE 34D substituting 3-(trifluoromethoxy)phenylboronic acid forphenyl boronic acid. MS (ESI) m/e 428.0 (M+H)⁺.

Example 35B4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-6-(3-(trifluoromethoxy)phenyl)pyridin-2(1H)-one

To a solution EXAMPLE 35A (0.065 g, 0.152 mmol) in 1 mL dichloromethanewas added trifluoroacetic acid (1 mL) and the solution stirred at roomtemperature for 1 hour. The solvent was removed and the crude materialdried over high-vacuum for several hours to give the title compound asthe trifluoroacetate salt. MS (ESI) m/e 371.9 (M+H)⁺; ¹H NMR (DMSO-d₆) δ6.83 (s, 1H), 7.13-7.37 (m, 2H), 7.48 (d, J=8.14 Hz, 1H), 7.65 (t,J=7.97 Hz, 1H), 7.80-8.12 (m, 2H), 8.21-8.55 (m, 3H), 12.31 (s, 1H).

Example 364-(1H-pynolo[2,3-b]pyridin-3-yl)-6-[3-(trifluoromethyl)phenyl]pyridin-2(1H)-oneExample 36A3-(2-tert-butoxy-6-(3-(trifluoromethyl)phenyl)pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

The title compound was prepared using the procedure described forEXAMPLE 34D substituting 3-(trifluoromethyl)phenylboronic acid forphenyl boronic acid. MS (ESI) m/e 428.0 (M+H)⁺.

Example 36B4-(1H-pynolo[2,3-b]pyridin-3-yl)-6-(3-(trifluoromethyl)phenyl)pyridin-2(1H)-one

The title compound was prepared as the trifluoroacetate salt using theprocedure described for EXAMPLE 35B substituting EXAMPLE 36A for EXAMPLE35A. MS (ESI) m/e 355.9 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 6.85 (d, J=1.36 Hz,1H), 7.25 (dd, J=7.97, 4.58 Hz, 2H), 7.35 (s, 1H), 7.63-7.94 (m, 3H),8.15-8.53 (m, 3H), 12.33 (s, 1H).

Example 376-(2,3-dimethylphenyl)-4-(1H-pynolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-oneExample 37A3-(2-tert-butoxy-6-(2,3-dimethylphenyl)pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

The title compound was prepared using the procedure described forEXAMPLE 34D substituting 2,3-dimethylphenylboronic acid for phenylboronic acid. MS (ESI) m/e 372.0 (M+H)⁺.

Example 37B6-(2,3-dimethylphenyl)-4-(1H-pynolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one

The title compound was prepared as the trifluoroacetate salt using theprocedure described for EXAMPLE 35B substituting EXAMPLE 37A for EXAMPLE35A. MS (ESI) m/e 315.9 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 2.21 (s, 3H), 2.32(s, 3H), 6.74 (d, J=1.70 Hz, 1H), 6.81 (d, J=1.36 Hz, 1H), 7.09-7.44 (m,5H), 8.15-8.54 (m, 3H), 12.38 (d, J=2.03 Hz, 1H).

Example 386-(2-methylphenyl)-4-(1H-pynolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-oneExample 38A3-(2-tert-butoxy-6-o-tolylpyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

The title compound was prepared using the procedure described forEXAMPLE 34D substituting 2-methylphenyl boronic acid for phenyl boronicacid. MS (ESI) m/e 358.0 (M+H)⁺

Example 38B 4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-6-o-tolylpyridin-2(1H)-one

The title compound was prepared as the trifluoroacetate salt using theprocedure described for EXAMPLE 35B substituting EXAMPLE 38A for EXAMPLE35A. MS (ESI) m/e 301.9 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 2.35 (s, 3H), 6.74(d, J=1.70 Hz, 1H), 6.78 (d, J=1.70 Hz, 1H), 7.24 (dd, J=7.80, 4.75 Hz,1H), 7.29-7.46 (m, 4H), 8.08-8.53 (m, 3H), 12.36 (s, 1H).

Example 396-(1,3-benzodioxol-5-yl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-oneExample 39A3-(2-(benzo[d][1,3]dioxol-5-yl)-6-tert-butoxypyridin-4-yl)-1H-pynolo[2,3-b]pyridine

The title compound was prepared using the procedure described forEXAMPLE 34D substituting benzo[d][1,3]dioxol-5-ylboronic acid for phenylboronic acid. MS (ESI) m/e 388.0 (M+H)⁺.

Example 39B6-(benzo[d][1,3]dioxol-5-yl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one

The title compound was prepared as the trifluoroacetate salt using theprocedure described for EXAMPLE 35B substituting EXAMPLE 39A for EXAMPLE35A. MS (ESI) m/e 331.9 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 6.07-6.19 (m, 2H),6.74 (d, J=1.70 Hz, 1H), 7.05 (s, 1H), 7.07 (s, 1H), 7.25 (dd, J=8.14,4.75 Hz, 1H), 7.44 (dd, J=8.14, 2.03 Hz, 1H), 7.52 (d, J=2.03 Hz, 1H),8.07-8.54 (m, 3H), 12.36 (s, 1H).

Example 404-(1H-pyrrolo[2,3-b]pyridin-3-yl)-6-(3-thienyl)pyridin-2(1H)-one Example40A3-(2-tert-butoxy-6-(thiophen-3-yl)pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

The title compound was prepared using the procedure described forEXAMPLE 34D substituting thiophen-3-ylboronic acid for phenyl boronicacid. MS (ESI) m/e 350.0 (M+H)⁺.

Example 40B4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-6-(thiophen-3-yl)pyridin-2(1H)-one

The title compound was prepared as the trifluoroacetate salt using theprocedure described for EXAMPLE 35B substituting EXAMPLE 40A for EXAMPLE35A. MS (ESI) m/e 293.8 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 6.72 (d, J=1.70 Hz,1H), 7.20 (d, J=1.36 Hz, 1H), 7.26 (dd, J=8.14, 4.75 Hz, 1H), 7.73 (dd,J=5.09, 3.05 Hz, 1H), 7.84 (dd, J=5.09, 1.36 Hz, 1H), 8.19-8.50 (m, 4H),12.40 (s, 1H).

Example 416-(2-naphthyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-oneExample 41A3-(2-tert-butoxy-6-(naphthalen-2-yl)-1,2-dihydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

The title compound was prepared using the procedure described forEXAMPLE 34D substituting naphthalen-2-ylboronic acid for phenyl boronicacid. MS (ESI) m/e 394.0 (M+H)⁺.

Example 41B6-(naphthalen-2-yl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one

The title compound was prepared as the trifluoroacetate salt using theprocedure described for EXAMPLE 35B substituting EXAMPLE 41A for EXAMPLE35A. MS (ESI) m/e 338.0 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 6.82 (d, J=1.59 Hz,1H), 7.19-7.37 (m, 2H), 7.61 (dd, J=6.35, 3.17 Hz, 2H), 7.92-8.12 (m,4H), 8.35 (d, J=3.17 Hz, 1H), 8.38-8.48 (m, 2H), 8.51 (s, 1H),12.19-12.57 (m, 1H).

Example 426-(3-chlorophenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-oneExample 42A3-(2-tert-butoxy-6-(3-chlorophenyl)-1,2-dihydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

The title compound was prepared using the procedure described forEXAMPLE 34D substituting 3-chlorophenylboronic acid for phenyl boronicacid. MS (ESI) m/e 378.0 (M+H)⁺.

Example 42B6-(3-chlorophenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one

The title compound was prepared as the trifluoroacetate salt using theprocedure described for EXAMPLE 35B substituting EXAMPLE 42A for EXAMPLE35A. MS (ESI) m/e 321.9 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 6.79 (s, 1H), 7.23(dd, J=7.93, 4.76Hz, 2H), 7.53 (t, J=4.76 Hz, 2H), 7.82-7.97 (m, 1H),8.03 (s, 1H), 8.19-8.51 (m, 3H), 12.28 (s, 1H).

Example 436-(2,3-dimethoxyphenyl)-4-(1H-pynolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-oneExample 43A3-(2-tert-butoxy-6-(2,3-dimethoxyphenyl)-1,2-dihydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

The title compound was prepared using the procedure described forEXAMPLE 34D substituting 2,3 dimethoxyphenylboronic acid for phenylboronic acid. MS (ESI) m/e 404.1 (M+H)⁺.

Example 43B6-(2,3-dimethoxyphenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one

The title compound was prepared as the trifluoroacetate salt using theprocedure described for EXAMPLE 35B substituting EXAMPLE 43A for EXAMPLE35A. MS (ESI) m/e 347.9 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 3.68-3.76 (m, 3H),3.84-3.91 (m, 3H), 6.89 (s, 1H), 6.99 (d, J=1.59 Hz, 1H), 7.11 (dd,J=6.35, 2.78 Hz, 1H), 7.18-7.24 (m, 2H), 7.27 (dd, J=7.93, 4.76 Hz, 1H),8.25-8.45 (m, 3H), 12.42 (s, 1H).

Example 446-(2-fluoro-3-methoxyphenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-oneExample 44A3-(2-tert-butoxy-6-(2-fluoro-3-methoxyphenyl)pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

The title compound was prepared using the procedure described forEXAMPLE 34D substituting 2-fluoro-3-methoxyphenylboronic acid for phenylboronic acid. MS (ESI) m/e 392.0 (M+H)⁺.

Example 44B6-(2-fluoro-3-methoxyphenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one

The title compound was prepared as the trifluoroacetate salt using theprocedure described for EXAMPLE 35B substituting EXAMPLE 44A for EXAMPLE35A. MS (ESI) m/e 335.9 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 3.90 (s, 3H),6.64-6.83 (m, 1H), 6.90 (s, 1H), 7.06-7.47 (m, 4H), 8.09-8.54 (m, 3H),12.30 (s, 1H).

Example 456-(4-chloro-2-fluorophenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-oneExample 45A3-(2-tert-butoxy-6-(4-chloro-2-fluorophenyl)pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

The title compound was prepared using the procedure described forEXAMPLE 34D substituting 2-fluoro-4-chlorophenylboronic acid for phenylboronic acid. MS (ESI) m/e 396.0 (M+H)⁺.

Example 45B6-(4-chloro-2-fluorophenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one

The title compound was prepared as the trifluoroacetate salt using theprocedure described for EXAMPLE 35B substituting EXAMPLE 45A for EXAMPLE35A. MS (ESI) m/e 339.9 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 6.77 (s, 1H), 6.95(s, 1H), 7.22 (dd, J=7.93, 4.76 Hz, 1H), 7.45 (dd, J=8.53, 1.78 Hz, 1H),7.63 (dd, J=10.31, 1.98 Hz, 1H), 7.76 (t, J=8.33 Hz, 1H), 8.23 (d,J=2.78 Hz, 1H), 8.27-8.41 (m, 2H), 12.11-12.41 (m, 1H).

Example 466-[2-methoxy-5-(trifluoromethyl)phenyl]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-oneExample 46A3-(2-tert-butoxy-6-(2-methoxy-5-(trifluoromethyl)phenyl)pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

The title compound was prepared using the procedure described forEXAMPLE 34D substituting 2-methoxy-5-(trifluoromethyl)phenylboronic acidfor phenyl boronic acid. MS (ESI) m/e 442.1 (M+H)⁺.

Example 46B6-(2-methoxy-5-(trifluoromethyl)phenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one

The title compound was prepared as the trifluoroacetate salt using theprocedure described for EXAMPLE 35B substituting EXAMPLE 46A for EXAMPLE35A. MS (ESI) m/e 386.0 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 3.86-3.98 (m, 3H),6.73 (d, J=1.36 Hz, 1H), 6.88 (s, 1H), 7.23 (dd, J=7.80, 4.75 Hz, 1H),7.35 (d, J=9.16 Hz, 1H), 7.83 (d, J=6.10 Hz, 2H), 8.24 (d, J=2.71 Hz,1H), 8.28-8.39 (m, 2H), 12.27 (s, 1H).

Example 472′-methoxy-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2,3′-bipyridin-6(1H)-oneExample 47A3-(2-tert-butoxy-6-(2-methoxypyridin-3-yl)-1,2-dihydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

The title compound was prepared using the procedure described forEXAMPLE 34D substituting 2-methoxy-pyridin-3-ylboronic acid for phenylboronic acid. MS (ESI) m/e 375.0 (M+H)⁺.

Example 47B6-(2-methoxypyridin-3-yl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one

The title compound was prepared as the trifluoroacetate salt using theprocedure described for EXAMPLE 35B substituting EXAMPLE 47A for EXAMPLE35A. MS (ESI) m/e 318.9 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 3.84-4.03 (m, 3H),6.72 (s, 1H), 6.89 (s, 1H), 7.14 (dd, J=7.34, 4.96 Hz, 1H), 7.23 (dd,J=7.93, 4.76 Hz, 1H), 7.97 (dd, J=7.34, 1.78 Hz, 1H), 8.17-8.40 (m, 4H),12.28 (s, 1H).

Example 486-(3-chloro-2-methylphenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-oneExample 48A3-(2-tert-butoxy-6-(3-chloro-2-methylphenyl)-1,2-dihydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

The title compound was prepared using the procedure described forEXAMPLE 34D substituting 2-methyl-3-chlorophenylboronic acid forphenylboronic acid. MS (ESI) m/e 392.0 (M+H)⁺.

Example 48B6-(3-chloro-2-methylphenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one

The title compound was prepared as the trifluoroacetate salt using theprocedure described for EXAMPLE 35B substituting EXAMPLE 48A for EXAMPLE35A. MS (ESI) m/e 335.9 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 2.29-2.39 (m, 3H),6.62 (s, 1H), 6.70 (s, 1H), 7.21 (dd, J=8.14, 4.75 Hz, 1H), 7.29-7.44(m, 2H), 7.57 (dd, J=7.80, 1.70 Hz, 1H), 8.22 (d, J=2.71 Hz, 1H),8.26-8.39 (m, 2H), 11.55 (s, 1H), 12.22 (s, 1H).

Example 493′-chloro-2′-methoxy-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2,4′-bipyridin-6(1H)-oneExample 49A3-(6-tert-butoxy-3′-chloro-2′-methoxy-2,4′-bipyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

The title compound was prepared using the procedure described forEXAMPLE 34D substituting 3-chloro-2-methoxy-pyridin-4-ylboronic acid forphenylboronic acid. MS (ESI) m/e 549.1 (M+H)⁺.

Example 49B6-(3-chloro-2-methoxypyridin-4-yl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one

The title compound was prepared as the trifluoroacetate salt using theprocedure described for EXAMPLE 35B substituting EXAMPLE 49A for EXAMPLE35A. MS (ESI) m/e 352.9 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 4.01 (s, 3H), 6.80(s, 1H), 6.88 (s, 1H), 7.12-7.31 (m, 2H), 8.17-8.28 (m, 2H), 8.27-8.40(m, 2H), 12.27 (d, J=1.59 Hz, 1H).

Example 506-[3-(morpholin-4-yl)phenyl]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-oneExample 50A4-(3-(6-tert-butoxy-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,6-dihydropyridin-2-yl)phenyl)morpholine

The title compound was prepared using the procedure described forEXAMPLE 34D substituting 3-morpholinophenylboronic acid forphenylboronic acid. MS (ESI) m/e 429.2 (M+H)⁺.

Example 50B6-(3-morpholinophenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one

The title compound was prepared as the trifluoroacetate salt using theprocedure described for EXAMPLE 35B substituting EXAMPLE 50A for EXAMPLE35A. MS (ESI) m/e 373.0 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 3.22 (d, 4H), 3.77(d, 4H), 6.76 (d, J=1.59 Hz, 1H), 7.09 (s, 2H), 7.25 (dd, J=8.13, 4.56Hz, 1H), 7.29-7.43 (m, 3H), 8.14-8.56 (m, 3H), 12.36 (s, 1H).

Example 516-[3-(methylsulfonyl)phenyl]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-oneExample 51A3-(2-tert-butoxy-6-(3-(methylsulfonyl)phenyl)-1,2-dihydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

The title compound was prepared using the procedure described forEXAMPLE 34D substituting 3-(methylsulfonyl)phenylboronic acid forphenylboronic acid. MS (ESI) m/e 422.0 (M+H)⁺.

Example 51B6-(3-(methylsulfonyl)phenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one

The title compound was prepared as the trifluoroacetate salt using theprocedure described for EXAMPLE 35B substituting EXAMPLE 51A for EXAMPLE35A. MS (ESI) m/e 366.0 (M+H)⁺; ¹H NMR (DMSO-d₆) 6 3.15-3.44 (s, 3H),6.85 (s, 1H), 7.24 (dd, J=8.33, 4.76 Hz, 1H), 7.29-7.43 (m, 1H), 7.80(t, J=7.93 Hz, 1H), 8.01 (d, J=7.93 Hz, 1H), 8.23-8.49 (m, 5H), 12.31(s, 1H).

Example 526-(1H-pyrazol-4-yl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-oneExample 52A3-(2-tert-butoxy-6-(1H-pyrazol-4-yl)-1,2-dihydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

The title compound was prepared using the procedure described forEXAMPLE 34D substituting4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole forphenylboronic acid. MS (ESI) m/e 334.0 (M+H)⁺.

Example 52B6-(1H-pyrazol-4-yl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one

The title compound was prepared as the trifluoroacetate salt using theprocedure described for EXAMPLE 35B substituting EXAMPLE 52A for EXAMPLE35A. MS (ESI) m/e 277.9 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 6.61 (s, 1H), 7.09(d, J=1.59 Hz, 1H), 7.24 (dd, J=7.93, 4.76 Hz, 1H), 8.24-8.46 (m, 5H),12.34 (s, 1H).

Example 532′-methyl-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2,3′-bipyridin-6(1H)-oneExample 53A3-(2-tert-butoxy-6-(2-methylpyridin-3-yl)-1,2-dihydropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

The title compound was prepared using the procedure described forEXAMPLE 34D substituting 2-methylpyridin-3-yl boronic acid forphenylboronic acid and CombiPhos-Pd6 (CombiPhos Catalysts, Inc, Catalog#AC2) for dichlorobis (triphenylphosphine)-palladium (II). MS (DCI) m/e359.2 (M+H)⁺.

Example 53B6-(2-methylpyridin-3-yl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one

The title compound was prepared as the trifluoroacetate salt using theprocedure described for EXAMPLE 35B substituting EXAMPLE 53A for EXAMPLE35A. MS (ESI) m/e 302.9 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 2.65-2.78 (m, 3H),6.89 (d, J=1.36 Hz, 1H), 7.01 (s, 1H), 7.24 (dd, J=7.80, 4.75 Hz, 1H),7.82 (dd, J=7.97, 5.59 Hz, 1H), 8.27 (d, J=2.71 Hz, 1H), 8.30-8.36 (m,1H), 8.40 (d, J=8.14 Hz, 2H), 8.80 (dd, J=5.42, 1.70 Hz, 1H), 12.36 (s,1H).

Example 546-[(3-methoxyphenyl)amino]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one

EXAMPLE 34B (0.2 g, 0.45 mmol), 3-methoxyaniline (0.8 g, 6 5 mmol) andp-toluenesulfonic acid (0.086 g, 0.45 mmol) was heated to 150° C. for 30minutes in a CEM microwave @100 W. The crude material was diluted with asmall amount of dichloromethane and placed directly onto a silica gelcolumn and purified (Analogix 280, gradient elution, 2-10%methanol/dichloromethane) to give the title compound. MS (ESI) m/e 333.3(M+H)⁺; ¹H NMR (DMSO-d₆) δ 3.67-3.84 (m, 3H), 6.28 (s, 1H), 6.49 (d,J=6.71 Hz, 1H), 6.57 (s, 1H), 7.07-7.20 (m, 3H), 7.22 (s, 1H), 7.83 (d,J=2.44 Hz, 1H), 8.17-8.31 (m, 3H), 8.37 (s, 1H), 11.72 (s, 1H).

Example 55 6-anilino-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one

The title compound was prepared using the procedure described forEXAMPLE 54 substituting aniline for 3-methoxyaniline. MS (ESI) m/e 303.3(M+H)⁺; ¹H NMR (DMSO-d₆) δ 6.30 (s, 1H), 6.67 (s, 1H), 6.89 (s, 1H),7.13-7.33 (m, 4H), 7.66 (s, 1H), 7.97 (d, J=2.03 Hz, 1H), 8.29 (d,J=5.09 Hz, 2H), 8.75 (s, 1H), 10.08 (s, 1H), 12.05 (s, 1H)

Example 566-[(trans-4-aminocyclohexyl)amino]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-oneExample 56A3-(2,6-difluoropyridin-4-yl)-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine

A suspension of1-(phenylsulfonyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine(7.26 g, 18.9 mmol), 2,6-difluoro-4-iodopyridine (4.14 g, 17.2 mmol,Eur. J. Org. Chem., 2004, 1018 and Org. Lett. 2007, 5175),dichlorobis(triphenylphosphine) palladium(II) (0.482 g, 0.687 mmol) and1M aqueous sodium carbonate (13.7 mL, 13.7 mmol) indimethoxyethane/ethanol/water (7:2:3) (80 mL) was degassed and heated at80° C. for 1.5 hours. After cooling, the suspension was filtered, washedwith water and ether, and concentrated to give the crude title compound.The filtrate was diluted with water and extracted twice withdichloromethane. The combined organic layers were dried over magnesiumsulfate, filtered, concentrated, and purified using an ISCO Companionflash system eluting with dichloromethane/hexane (7:3 to 9:1) to givethe title compound. The combined products were used in the next stepwithout further purification.

Example 56B 3-(2,6-difluoropyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine

A mixture of EXAMPLE 56A (8.01 g, 21 6 mmol) and 20% aqueous sodiumhydroxide (12 mL, 21.6 mmol) in 1,4-dioxane (75 mL) was heated at 50° C.for 90 minutes. The mixture was concentrated and the residue trituratedwith water, filtered, and concentrated to give the title compound.

Example 56Ctrans-N¹-(6-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)cyclohexane-1,4-diamine

A mixture of EXAMPLE 56B (0.60 g, 2.60 mmol) andtrans-cyclohexane-1,4-diamine (1.04 g, 9.08 mmol) in ethanol (10 mL) washeated at in a Biotage Initiator microwave reactor at 170° C. for 80minutes. After concentration, the residue was treated with 20% brine andextracted twice with ethyl acetate. The combined organic layers wereconcentrated and purified on a 110 g silica column (KP-NH from Biotage)eluting with ethyl acetate/methanol (97:3 to 90:10) to give the titlecompound.

Example 56D6-(trans-4-aminocyclohexylamino)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one

A mixture of EXAMPLE 56C (0.500 g, 1.54 mmol) and concentrated HCl (0.80mL, 26.3 mmol) in tert-butanol (10 mL) was heated at 140° C. for 40minutes in a Biotage Initiator microwave reactor. The top layer wasdecanted and the viscous bottom layer was dissolved in methanol andtreated with saturated sodium bicarbonate until at a pH of 4. Thesolution was concentrated and the residue purified by reversed-phaseHPLC on a Zorbax RX-C18 column (250×21.2 mm, 7 μm particle size) using agradient of 10-100% acetonitrile/0.1% aqueous trifluoroacetic acid togive the title compound as the trifluoroacetic acid salt. MS (DCI) m/z324.2 (M+H)⁺. ¹H NMR (DMSO-d₆) δ 1.20-1.57 (m, 4H), 1.84-2.13 (m, 4H),2.94-3.14 (m, 1H), 3.51-3.69 (m, 1H), 6.29 (s, 1H), 6.44 (s, 1H), 7.24(dd, J=8.1, 4.7 Hz, 1H), 7.88 (d, J=4.3 Hz, 3H), 8.20 (d, J=2.8 Hz, 1H),8.27 (dd, J=8.2, 1.2 Hz, 1H), 8.33 (dd, J=4.6, 1.5 Hz, 1H), 12.38 (s,1H).

Example 57N-(trans-4-{[6-oxo-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,6-dihydropyridin-2-yl]amino}cyclohexyl)cyclopropanesulfonamide

A mixture of EXAMPLE 56D (70.0 mg, 0.127 mmol), triethylamine (0.088 mL,0.64 mmol) and cyclopropanesulfonyl chloride (0.014 mL, 0.14 mmol) inN,N-dimethylformamide (1.5 mL) was stirred at room temperature for 5hours. Water was added and the suspension was filtered and purified byreversed-phase HPLC to give the title compound as the trifluoroaceticacid salt. MS (DCI⁺) m/z 428.3 (M+H)⁺. ¹H NMR (DMSO-d₆) δ 0.89-0.98 (m,4H), 1.26-1.53 (m, 4H), 1.91-2.04 (m, 4H), 2.54-2.62 (m, 2H), 3.13-3.24(m, 1H), 6.30 (s, 1H), 6.53 (s, 1H), 7.14 (d, J=7.6 Hz, 1H), 7.27 (dd,J=7.9, 4.6 Hz, 1H), 8.24 (d, J=2.8 Hz, 1H), 8.28 (dd, J=8.1, 1.4 Hz,1H), 8.34 (dd, J=4.7, 1.4 Hz, 1H), 12.43 (s, 1H).

Example 58N-(trans-4-{[6-oxo-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,6-dihydropyridin-2-yl]amino}cyclohexyl)cyclopropanecarboxamide

A mixture of EXAMPLE 56D (70.0 mg, 0.127 mmol), triethylamine (0.088 mL,0.64 mmol), N-hydroxybenzotriazole (38.9 mg, 0.254 mmol),1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (48.7 mg,0.254 mmol) and cyclopropanecarboxylic acid (0.012 mL, 0.15 mmol) intetrahydrofuran (2 mL) was stirred at room temperature for 5 hours. Themixture was concentrated and purified by reversed-phase HPLC to give thetitle compound as a trifluoroacetic acid salt. MS (DCL) m/z 392.2(M+H)⁺; ¹H NMR (CD₃OD) δ 0.69-0.77 (m, 2H), 0.80-0.88 (m, 2H), 1.41-1.61(m, 5H), 1.95-2.06 (m, 2H), 2.09-2.20 (m, 2H), 3.59-3.75 (m, 2H), 4.80(s, 1H), 4.91 (s, 1H), 7.34 (dd, J=7.9, 4.9 Hz, 1H), 8.10 (s, 1H), 8.36(dd, J=4.9, 1.2 Hz, 1H), 8.41 (dd, J=8.1, 1.4 Hz, 1H).

Example 591-(4-fluorobenzyl)-N-(trans-4-{[6-oxo-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,6-dihydropyridin-2-yl]amino}cyclohexyl)azetidine-3-carboxamide

A mixture of EXAMPLE 56D (70.0 mg, 0.127 mmol), triethylamine (0.088 mL,0.64 mmol), N-hydroxybenzotriazole (38.9 mg, 0.254 mmol),1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (48.7 mg,0.254 mmol) and 1-(4-fluorobenzyl)azetidine-3-carboxylic acid (31.9 mg,0.152 mmol) in tetrahydrofuran (2 mL) was stirred at room temperaturefor 5 hours. The reaction mixture was concentrated and purified byreversed-phase HPLC to give the title compound as a trifluoroacetic acidsalt. MS (APCL) m/z 515.5 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 1.23-1.46 (m, 4H),1.74-1.93 (m, 2H), 1.94-2.09 (m, 2H), 3.38-4.30 (m, 7H), 4.37 (s, 2H),6.28 (s, 1H), 6.44 (s, 1H), 7.17 (s, brd, 1H), 7.24 (dd, J=8.1, 4.7 Hz,1H), 7.30 (t, J=8.9 Hz, 2H), 7.54 (dd, J=8.7, 5.3 Hz, 2H), 8.14 (d,J=7.6 Hz, 1H), 8.20 (d, J=1.8 Hz, 1H), 8.27 (d, J=7.6 Hz, 1H), 8.33 (dd,J=4.7, 1.4 Hz, 1H), 10.30 (s, brd, 1H), 12.39 (s, 1H).

Example 602-(4-methylphenyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared using the procedure described forEXAMPLE 32 replacing phenylmagnesium bromide with p-tolylmagnesiumbromide. MS (ESI) m/e 303 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 2.41 (s, 3H), 6.74(s, 1H), 7.24 (dd, J=7.93, 4.88 Hz, 1H), 7.39 (d, J=7.93 Hz, 2H), 8.17(d, J=7.63 Hz, 2H), 8.31 (dd, J=4.58, 1.53 Hz, 1H), 8.42 (d, J=1.22 Hz,1H), 8.70 (d, J=7.32 Hz, 1H), 12.31 (s, 1H).

Example 612-(3-methylphenyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared using the procedure described forEXAMPLE 32 replacing phenylmagnesium bromide with m-tolylmagnesiumbromide. MS (ESI) m/e 303 (M+H)⁺; ¹H NMR (DMSO-d₆) δ 2.44 (s, 3H), 6.76(s, 1H), 7.25 (dd, J=7.93, 4.88 Hz, 1H), 7.39-7.53 (m, 2H), 8.02-8.14(m, 2H), 8.31 (dd, J=4.58, 1.53 Hz, 1H), 8.43 (s, 1H), 8.69 (d, J=7.93Hz, 1H), 12.28 (s, 1H).

Example 62 Chunqiu Lai2-(2,3-dimethylphenyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

The title compound was prepared using the procedure described forEXAMPLE 32 replacing phenylmagnesium bromide with(2,3-dimethylphenyl)magnesium bromide. MS (ESI) m/e 317 (M+H)⁺; ¹H NMR(DMSO-d₆) δ 2.29 (s, 3H), 2.34 (s, 3H), 6.73 (s, 1H), 7.16 (dd, J=7.93,4.88 Hz, 1H), 7.25 (t, J=7.48 Hz, 1H), 7.32-7.38 (m, 2H), 8.27 (dd,J=4.73, 1.37 Hz, 1H), 8.31 (s, 1H), 8.54 (d, J=7.93 Hz, 1H), 12.27 (s,1H).

Example 632-{[3-(3-aminopropoxy)benzyl]amino}-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-oneExample 63A3-((4-methoxy-6-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-ylamino)methyl)phenol

Example 1B (889 mg, 2.00 mmol), 3-(aminomethyl)phenol (739 mg, 6.00mmol), triethylamine (0.836 ml, 6.00 mmol) and dioxane (8 ml) wereplaced in a pressure tube. The mixture was heated at 100° C. overnight.The cooled reaction mixture was concentrated in vacuo. Flashchromatography (gradient elution, ethyl acetate/hexane 5-50%) gave thetitle compound.

Example 63B tert-butyl3-(3-((4-methoxy-6-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-ylamino)methyl)phenoxy)propylcarbamate

To a mixture of Example 63A (0.510 g, 1.05 mmol), tert-butyl3-hydroxypropylcarbamate (0.275 g, 1.57 mmol) and triphenylphosphine(0.412 g, 1.57 mmol) in tetrahydrofuran (13 ml) was added dropwisediisopropyl azodicarboxylate (DIAD) (0.305 ml, 1.57 mmol). The reactionmixture was stirred at room temperature for 3 hours and thenconcentrated in vacuo. Flash chromatography isolation (gradient elution,ethyl acetate/hexane 0-50%) gave the title compound.

Example 63C tert-butyl3-(3-((4-methoxy-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-ylamino)methyl)phenoxy)propylcarbamate

A mixture of Example 63B (600 mg, 0.93 mmol) in methanol (12 mL) andNaOH aqueous solution (1M, 4 mL) was stirred at room temperature for 16hours. The mixture was filtered, and the solid was washed with water anddried in vacuo to give the title compound.

Example 63D2-(3-(3-aminopropoxy)benzylamino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one

To Example 63C (297 mg, 0.59 mmol) was added aqueous HCl (12 M, 8.0 ml)and the mixture was heated at 90° C. for 5 hours. The cooled reactionmixture was concentrated in vacuo to give the title compound as an HClsalt. MS (ESI) m/e 391(M+H)⁺; ¹H NMR (300 MHz, DMSO-d₆) δ ppm 1.94-2.11(m, 1H) 2.86-3.02 (m, 2H) 4.00-4.11 (m, 2H) 4.58-4.73 (m, 2H) 6.12-6.53(m, 1H) 6.87 (d, J=8.82 Hz, 1H) 6.96-7.06 (m, 2H) 7.16-7.37 (m, 2H)7.82-8.10 (m, 3H) 8.35 (s, 1H) 8.50 (d, J=7.80 Hz, 1H) 12.63 (s, 1H).

Example 68 Enzyme Inhibition Data

This example describes the assays that may be used to identify compoundshaving kinase activity.

Cdc7 (BEV coexpressed huCDC7/DBF4) is prepared internally. Cdc7 assaysare conducted as follows with final concentrations as listed. In384-well v-bottom polypropylene plates, 6 μL compound (2% DMSO), ismixed with 6 μL of Cdc7 (2 ug/mL), and Jerini peptide substrate A-A11(biotin-C₆linker-TPSDSLIYDDGLS) (2 μM), followed by immediate initiationwith 6 μL λ-[³³P]-ATP (1 μM, 20 mCi/μmol) using a reaction buffercomprising 25 mM HEPES, pH 7.5, 1 mM DTT, 10 mM MgCl₂, 100 μM, Na₃VO₄,0.075 mg/ml Triton X-100. Reactions are quenched after 1 hr by theaddition of 90 μL stop buffer (50 mM EDTA, 2M NaCl). 85 μL of thestopped reactions are transferred to 384-well streptavidin-coated plates(FlashPlate Plus, Perkin Elmer), incubated 30 minutes at roomtemperature and washed 3 times with 0.05% Tween-20/PBS using an ELX-405automated plate washer (BioTek), and counted on a TopCount ScintillationPlate Reader (Packard). IC50 values are determined via non-linearregression fitting of enzyme inhibition data and corresponding Ki valuesare generated assuming ATP-competitive (equilibrium) inhibition andusing the experimentally determined apparent ATP Km of 0.7 μM (asdetermined using the above assay condition, but varying ATP).

Table 1 depicts enzyme inhibition data (K,) for exemplary compounds. InTable 1, “A” represents a K_(i) of less than 10 nM and “B” represents aK_(i) of between 10 nM and 100 nM.

TABLE 1 Example Cdc7 Inhibition Example CDC-7 Inhibition  1 A 33 A  2 A34 A  3 A 35 A  4 A 36 A  5 A 37 A  6 A 38 A  7 A 39 A  8 A 40 A  9 A 41A 10 A 42 A 11 A 43 A 12 A 44 A 13 A 45 A 14 A 46 A 15 A 47 A 16 A 48 A17 A 49 A 18 A 50 A 19 A 51 A 20 A 52 A 21 A 53 A 22 A 54 A 23 A 55 A 24A 56 A 25 A 57 A 26 A 58 A 27 A 59 A 28 A 60 A 29 A 61 A 30 A 62 A 31 A63 A 32 A

Compounds of the present invention assessed by the above-describedassays were found to have Cdc7 kinase-inhibiting activity.

All publication and patent applications cited in this specification areherein incorporated by reference as if each individual publication orpatent application were specifically and individually indicated to beincorporated by reference. Although the foregoing invention has beendescribed in some detail by way of illustration and example for purposesof clarity of understanding, it will be readily apparent to those ofordinary skill in the art in light of the teachings of this inventionthat certain changes and modifications may be made thereto withoutdeparting from the spirit or scope of the appended claims.

1. A compound having formula (I)

wherein R^(1a), R^(1b), and R^(1c) are independently hydrogen, hydroxy,nitro, halogen, cyano, trifluoromethyl, trifluoromethoxy, C₁₋₄-alkyl,—OR^(a), —NR^(b)R^(c); —C(O)OR^(a), —C(O)NR^(b)R^(c), —NR^(b)C(O)R^(c),—NHC(O)NHR^(b), or —NHSO₂R^(a); X is N or CR²; R² is hydrogen orC₁₋₄-alkyl; Y is NR³R⁴, NR⁶C(O)R⁷, NR⁶SO₂R⁷, aryl, or heterocyclyl,wherein the aryl and heterocyclyl are optionally substituted with one ormore R⁵; R³ is hydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,C₃₋₈-cycloalkyl, C₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, heterocycloalkyl,heterocycloalkyl-(C₁₋₈-alkyl)-, aryl, aryl-(C₁₋₈-alkyl)-, heteroaryl-,or heteroaryl-(C₁₋₈-alkyl)-, wherein (a) the R³ C₁₋₈-alkyl,C₂₋₈-alkenyl, C₂₋₈-alkynyl substituents, alone or as part of anothergroup, are optionally substituted with one or more substituents selectedfrom the group consisting of halogen, cyano, nitro, —OR^(a), —C(O)R^(a),—C(O)OR^(a), —OC(O)R^(a), —NR^(b)R^(c), —NR^(b)C(O)R^(a),—NHC(O)NHR^(b), —C(O)NR^(b)R^(c), —NHSO₂R^(a), —SO₂NR^(b)NR^(c), andaryl; and (b) the R³ C₃₋₈-cycloalkyl, heterocycloalkyl, aryl, andheteroaryl, alone or as part of another group, are optionallysubstituted with one or more R⁵; R⁴ is hydrogen or C₁₋₈-alkyl; whereinthe C₁₋₈-alkyl is optionally substituted with one or more substituentsselected from the group consisting of halogen, cyano, —OR^(a),—C(O)R^(a), —C(O)OR^(a), —OC(O)R^(a), —NR^(b)R^(c), —NR^(b)C(O)R^(a),—NHC(O)NHR^(b), —C(O)NR^(b)R^(c), —NHSO₂R^(a), and —SO₂NR^(b)NR^(c); R⁵is selected from the group consisting of C₁₋₈-alkyl, C₂₋₈-alkenyl,C₂₋₈-alkynyl, aryl, heterocyclyl, halogen, cyano, nitro, —OR^(d),—C(O)R^(d), —C(O)OR^(d), —OC(O)R^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d),—NHC(O)NHR^(e), —NHSO₂R^(e), —C(O)NR^(e)R^(f), —SR^(d), —S(O)R^(d),—SO₂R^(d), —SO₂NR^(e)NR^(f), —B(OH)₂, —CF₃, —CF₂CF₃, —OCF₃, and —OCF₂CF₃wherein (a) the R⁵ C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, substituentsare optionally substituted with one or more substituents selected fromthe group consisting of aryl, heterocyclyl, C₃₋₈-cycloalkyl, halogen,cyano, nitro, —OR^(d), —C(O)R^(d), —C(O)OR^(d), —OC(O)R^(d),—NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHC(O)NHR^(e), —C(O)NR^(e)R^(f); andwherein (b) the R⁵ aryl or heterocyclyl substituents are optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl,heterocyclyl, halogen, cyano, nitro, —OR^(g), —C(O)R^(g), —C(O)OR^(g),—OC(O)R^(g), —NR^(h)R^(i), —NR^(h)C(O)R^(g), —NHC(O)NHR^(h),—NHSO₂R^(g), —C(O)NR^(h)R^(i), —SR^(g), —S(O)R^(g), —SO₂R^(g),—SO₂NR^(h)NR^(i), —CF₃, —CF₂CF₃, —OCF₃, and —OCF₂CF₃; R⁶ is hydrogen orC₁₋₈-alkyl; R⁷ is C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl,C₃₋₈-cycloalkyl, C₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, heterocycloalkyl,heterocycloalkyl-(C₁₋₈-alkyl)-, aryl, aryl-(C₁₋₈-alkyl)-, heteroaryl-,or heteroaryl-(C₁₋₈-alkyl)-, wherein (a) the R⁷ C₁₋₈-alkyl,C₂₋₈-alkenyl, C₂₋₈-alkynyl substituents, alone or as part of anothergroup, are optionally substituted with one or more substituents selectedfrom the group consisting of halogen, cyano, nitro, —OR^(a), —C(O)R^(a),—C(O)OR^(a), —OC(O)R^(a), —NR^(b)R^(c), —NR^(b)C(O)R^(a),—NHC(O)NHR^(b), —C(O)NR^(b)R^(c), —NHSO₂R^(a), —SO₂NR^(b)NR^(c), andaryl; and (b) the R⁷ C₃₋₈-cycloalkyl, heterocycloalkyl, aryl, andheteroaryl, alone or as part of another group, are optionallysubstituted with one or more R⁵; R^(a), at each occurrence, is selectedfrom the group consisting of hydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl,C₂₋₈-alkynyl, aryl, heterocyclyl, and C₃₋₈-cycloalkyl, wherein theC₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl, andC₃₋₈-cycloalkyl are optionally substituted with one or more substituentsindependently selected from the group consisting of C₁₋₈-alkyl, aryl,heterocyclyl, C₃₋₈-cycloalkyl, halogen, cyano, hydroxy, C₁₋₈-alkoxy,—NH₂, —NH(C₁₋₈-alkyl), —O(C₁₋₈-alkyl)NH₂, and —N(C₁₋₈-alkyl)₂; R^(b) andR^(c), at each occurrence, are independently selected from the groupconsisting of hydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl,heterocyclyl, and C₃₋₈-cycloalkyl, and optionally, R^(b) and R^(c) canbe joined together to form a 4-7 membered heterocycloalkyl ring, whereinthe C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,C₃₋₈-cycloalkyl, and 4-7 membered heterocycloalkyl ring are optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl,halogen, cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and—N(C₁₋₈-alkyl)₂; R^(d), at each occurrence, is selected from the groupconsisting of hydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl,heterocyclyl, and C₃₋₈-cycloalkyl, wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl,C₂₋₈-alkynyl, aryl, heterocyclyl, and C₃₋₈-cycloalkyl are optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, aryl, aryl-(C₁₋₈-alkyl)-,heterocyclyl, C₃₋₈-cycloalkyl, halogen, cyano, oxo, hydroxy,C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and —N(C₁₋₈-alkyl)₂; wherein thearyl, aryl-(C₁₋₈-alkyl), heterocyclyl, and C₃₋₈-cycloalkyl, alone or aspart of another group, are optionally substituted with one or moresubstituents independently selected from the group consisting ofC₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl, halogen, cyano,hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and —N(C₁₋₈-alkyl)₂; R^(e)and R^(f), at each occurrence, are independently selected from the groupconsisting of hydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl,heterocyclyl, and C₃₋₈-cycloalkyl, and optionally, R^(e) and R^(f) canbe joined together to form a 4-7 membered heterocycloalkyl ring, whereinthe C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl,C₃₋₈-cycloalkyl, and 4-7 membered heterocycloalkyl ring are optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl,halogen, cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and—N(C₁₋₈-alkyl)₂; R^(g), at each occurrence, is selected from the groupconsisting of hydrogen, C₁₋₈-alkyl, C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl,heterocyclyl, and C₃₋₈-cycloalkyl, wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl,C₂₋₈-alkynyl, aryl, heterocyclyl, and C₃₋₈-cycloalkyl are optionallysubstituted with one or more substituents independently selected fromthe group consisting of C₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl,halogen, cyano, hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and—N(C₁₋₈-alkyl)₂; R^(h) and R^(i), at each occurrence, are independentlyselected from the group consisting of hydrogen, C₁₋₈-alkyl,C₂₋₈-alkenyl, C₂₋₈-alkynyl, aryl, heterocyclyl, and C₃₋₈-cycloalkyl, andoptionally, R^(h) and R^(i) can be joined together to form a 4-7membered heterocycloalkyl ring, wherein the C₁₋₈-alkyl, C₂₋₈-alkenyl,C₂₋₈-alkynyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl, and 4-7 memberedheterocycloalkyl ring are optionally substituted with one or moresubstituents independently selected from the group consisting ofC₁₋₈-alkyl, aryl, heterocyclyl, C₃₋₈-cycloalkyl, halogen, cyano,hydroxy, C₁₋₈-alkoxy, —NH₂, —NH(C₁₋₈-alkyl), and —N(C₁₋₈-alkyl)₂; or apharmaceutically acceptable salt thereof.
 2. The compound of claim 1,wherein R^(1a), R^(1b), and R^(1c) are hydrogen.
 3. The compound ofclaim 1, wherein X is N.
 4. The compound of claim 1, wherein X is CR²and R² is hydrogen.
 5. The compound of claim 1, wherein Y is NR³R⁴. 6.The compound of claim 5, wherein R³ is C₁₋₈-alkyl, wherein theC₁₋₈-alkyl is optionally substituted with one or two R⁵.
 7. The compoundof claim 5, wherein R³ is aryl or heteroaryl, wherein the aryl andheteroaryl are optionally substituted with one or more R⁵.
 8. Thecompound of claim 5, wherein R³ is C₃₋₈-cycloalkyl or heterocycloalkyl,wherein the C₃₋₈-cycloalkyl or heterocycloalkyl are optionallysubstituted with one or more R⁵.
 9. The compound of claim 5, wherein R³is C₃₋₈-cycloalkyl-(C₁₋₈-alkyl)-, heterocycloalkyl-(C₁₋₈-alkyl)-,aryl-(C₁₋₈-alkyl)-, or heteroaryl-(C₁₋₈-alkyl)-, wherein the R³C₃₋₈-cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionallysubstituted with one or more R⁵.
 10. The compound of claim 5, wherein R⁴is hydrogen or methyl.
 11. The compound of claim 1, wherein Y isheterocyclyl, wherein the heterocyclyl is optionally substituted withone or more R⁵.
 12. The compound of claim 1, wherein Y is aryl, whereinthe aryl is optionally with one or more R⁵.
 13. The compound of claim 1wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is N, Y is NR³R⁴,wherein R³ is C₃₋₈-cycloalkyl, wherein the C₃₋₈-cycloalkyl is optionallysubstituted with one or two substituents independently selected from thegroup consisting of C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d),—C(O)OR^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d),—CF₃, and —OCF₃ wherein the C₁₋₈-alkyl is optionally substituted withone or more —OR^(d), and wherein R^(d), R^(e), and R^(f) areindependently selected from the group consisting of hydrogen,C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.
 14. The compound of claim 1 whereinR^(1a), R^(1b), and R^(1c) are hydrogen, X is is CR², R² is hydrogen, Yis NR³R⁴, wherein R³ is C₃₋₈-cycloalkyl, wherein the C₃₋₈-cycloalkyl isoptionally substituted with one or two substituents independentlyselected from the group consisting of C₁₋₈-alkyl, heterocyclyl, halogen,—OR^(d), —C(O)OR^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e),—SO₂R^(d), —CF₃, and —OCF₃ wherein the C₁₋₈-alkyl is optionallysubstituted with one or more —OR^(d), wherein R⁴ is hydrogen orC₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) are independentlyselected from the group consisting of hydrogen, C₁₋₈-alkyl, andC₃₋₈-cycloalkyl.
 15. The compound of claim 1 wherein R^(1a), R^(1b), andR^(1c) are hydrogen, X is N, Y is NR³R⁴, wherein R³ is aryl, wherein thearyl is optionally substituted with one or two substituentsindependently selected from the group consisting of C₁₋₈-alkyl,heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃ wherein theC₁₋₈-alkyl is optionally substituted with one or more —OR^(d), whereinR⁴ is hydrogen or C₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) areindependently selected from the group consisting of hydrogen,C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.
 16. The compound of claim 1 whereinR^(1a), R^(1b), and R^(1c) are hydrogen, X is is CR², R² is hydrogen, Yis NR³R⁴, wherein R³ is aryl, wherein the aryl is optionally substitutedwith one or two substituents independently selected from the groupconsisting of C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d),—NR^(e)R^(f), —NR^(c)C(O)R^(d), —NHSO₂R^(c), —SO₂R^(d), —CF₃, and —OCF₃wherein the C₁₋₈-alkyl is optionally substituted with one or more—OR^(d), wherein R⁴ is hydrogen or C₁₋₈-alkyl, and wherein R^(d), R^(e),and R^(f) are independently selected from the group consisting ofhydrogen, C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.
 17. The compound of claim 1wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is N, Y is NR³R⁴,wherein R³ is aryl-(C₁₋₈-alkyl), wherein the aryl is optionallysubstituted with one or two substituents independently selected from thegroup consisting of C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d),—C(O)OR^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d),—CF₃, and —OCF₃ wherein the C₁₋₈-alkyl is optionally substituted withone or more —OR^(d), wherein R⁴ is hydrogen or C₁₋₈-alkyl, and whereinR^(d), R^(e), and R^(f) are independently selected from the groupconsisting of hydrogen, C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.
 18. Thecompound of claim 1 wherein R^(1a), R^(1b), and R^(1c) are hydrogen, Xis N, Y is NR³R⁴, wherein R³ is heterocycloalkyl, wherein theheterocycloalkyl is optionally substituted with one or two substituentsindependently selected from the group consisting of C₁₋₈-alkyl,heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(c)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃ wherein theC₁₋₈-alkyl is optionally substituted with one or more —OR^(d), whereinR⁴ is hydrogen or C₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) areindependently selected from the group consisting of hydrogen,C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.
 29. The compound of claim 1 whereinR^(1a), R^(1b), and R^(1c) are hydrogen, X is N, Y is NR³R⁴, wherein R³is heterocycloalkyl-(C₁₋₈-alkyl)-, wherein the heterocycloalkyl isoptionally substituted with one or two substituents independentlyselected from the group consisting of C₁₋₈-alkyl, heterocyclyl, halogen,—OR^(d), —C(O)OR^(d), —NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e),—SO₂R^(d), —CF₃, and —OCF₃ wherein the C₁₋₈-alkyl is optionallysubstituted with one or more —OR^(d), wherein R⁴ is hydrogen orC₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) are independentlyselected from the group consisting of hydrogen, C₁₋₈-alkyl, andC₃₋₈-cycloalkyl.
 20. The compound of claim 1 wherein R^(1a), R^(1b), andR^(1c) are hydrogen, X is is CR², R² is hydrogen, Y is heterocyclyl,wherein the heterocyclyl is optionally substituted with one or moresubstituents independently selected from the group consisting ofC₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃ wherein theC₁₋₈-alkyl is optionally substituted with one or more —OR^(d), whereinR⁴ is hydrogen or C₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) areindependently selected from the group consisting of hydrogen,C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.
 21. The compound of claim 1 whereinR^(1a), R^(1b), and R^(1c) are hydrogen, X is N, Y is heterocyclyl,wherein the heterocyclyl is optionally substituted with one or moresubstituents independently selected from the group consisting ofC₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃ wherein theC₁₋₈-alkyl is optionally substituted with one or more —OR^(d), whereinR⁴ is hydrogen or C₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) areindependently selected from the group consisting of hydrogen,C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.
 22. The compound of claim 1 whereinR^(1a), R^(1b), and R^(1c) are hydrogen, X is is CR², R² is hydrogen, Yis NR³R⁴, wherein R³ is C₁₋₈-alkyl, wherein the R³ C₁₋₈-alkyl isoptionally substituted with one or more substituents selected from thegroup consisting of halogen, —OR^(a), and —NR^(b)R^(c); wherein R⁴ ishydrogen or C₁₋₈-alkyl, and wherein R^(c), R^(d), R^(e), and R^(f) areindependently selected from the group consisting of hydrogen,C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.
 23. The compound of claim 1 whereinR^(1a), R^(1b), and R^(1c) are hydrogen, X is N, Y is NR³R⁴, wherein R³is heteroaryl-(C₁₋₈-alkyl)-, wherein the aryl is optionally substitutedwith one or two substituents independently selected from the groupconsisting of C₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d),—NR^(e)R^(f), —NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃wherein the C₁₋₈-alkyl is optionally substituted with one or more—OR^(d), wherein R⁴ is hydrogen or C₁₋₈-alkyl, and wherein R^(d), R^(e),and R^(f) are independently selected from the group consisting ofhydrogen, C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.
 24. The compound of claim 1wherein R^(1a), R^(1b), and R^(1c) are hydrogen, X is is CR², R² ishydrogen, Y is aryl, wherein the aryl is optionally substituted with oneor more substituents independently selected from the group consisting ofC₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃ wherein theC₁₋₈-alkyl is optionally substituted with one or more —OR^(d), whereinR⁴ is hydrogen or C₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) areindependently selected from the group consisting of hydrogen,C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.
 25. The compound of claim 1 whereinR^(1a), R^(1b), and R^(1c) are hydrogen, X is N, Y is aryl, wherein thearyl is optionally substituted with one or more substituentsindependently selected from the group consisting of C₁₋₈-alkyl,heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃ wherein theC₁₋₈-alkyl is optionally substituted with one or more —OR^(d), whereinR⁴ is hydrogen or C₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) areindependently selected from the group consisting of hydrogen,C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.
 26. The compound of claim 1 whereinR^(1a), R^(1b), and R^(1c) are hydrogen, X is is CR², R² is ydrogen, Yis heteroaryl, wherein the heteroaryl is optionally substituted with oneor more substituents independently selected from the group consisting ofC₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃ wherein theC₁₋₈-alkyl is optionally substituted with one or more —OR^(d), whereinR⁴ is hydrogen or C₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) areindependently selected from the group consisting of hydrogen,C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.
 27. The compound of claim 1 whereinR^(1a), R^(1b), and R^(1c) are hydrogen, X is N, Y is heteroaryl,wherein the heteroaryl is optionally substituted with one or moresubstituents independently selected from the group consisting ofC₁₋₈-alkyl, heterocyclyl, halogen, —OR^(d), —C(O)OR^(d), —NR^(e)R^(f),—NR^(e)C(O)R^(d), —NHSO₂R^(e), —SO₂R^(d), —CF₃, and —OCF₃ wherein theC₁₋₈-alkyl is optionally substituted with one or more —OR^(d), whereinR⁴ is hydrogen or C₁₋₈-alkyl, and wherein R^(d), R^(e), and R^(f) areindependently selected from the group consisting of hydrogen,C₁₋₈-alkyl, and C₃₋₈-cycloalkyl.
 28. The compound of claim 1 which is2-(cyclohexylamino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-(benzylamino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-anilino-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-[(trans-4-aminocyclohexyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-[(3,5-difluorobenzyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-(piperidin-4-ylamino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-(4-hydroxypiperidin-1-yl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-{[(1S)-1-phenylethyl]amino}-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;6-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(tetrahydro-2H-pyran-4-ylamino)pyrimidin-4(3H)-one;6-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-[(tetrahydrofuran-2-ylmethyl)amino]pyrimidin-4(3H)-one;2-[cyclohexyl(methyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-{[(1R)-1-phenylethyl]amino}-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-[(2-aminocyclohexyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-(cycloheptylamino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;6-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(thiomorpholin-4-yl)pyrimidin-4(3H)-one;2-{[2-(methylamino)ethyl]amino}-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-[bis(2-methoxyethyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-[(2-methoxyethyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-[(2-hydroxyethyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;6-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-{[2-(trifluoromethyl)benzyl]amino}pyrimidin-4(3H)-one;2-[4-(hydroxymethyl)piperidin-1-yl]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-{[3-(morpholin-4-yl)propyl]amino}-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-[(3-hydroxybenzyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-(morpholin-4-yl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;1-[6-oxo-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,6-dihydropyrimidin-2-yl]piperidine-4-carboxylicacid;2-(cyclopentylamino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-(4-methoxypiperidin-1-yl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-[(2-hydroxycyclohexyl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-[(1-methylpiperidin-4-yl)amino]-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-{[3-(1H-imidazol-1-yl)propyl]amino}-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-({2-[2-(2-aminoethoxy)ethoxy]ethyl}amino)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-phenyl-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-(2-methylphenyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;6-phenyl-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-6-[3-(trifluoromethoxy)phenyl]pyridin-2(1H)-one;4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-6-[3-(trifluoromethyl)phenyl]pyridin-2(1H)-one;6-(2,3-dimethylphenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;6-(2-methylphenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;6-(1,3-benzodioxol-5-yl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-6-(3-thienyl)pyridin-2(1H)-one;6-(2-naphthyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;6-(3-chlorophenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;6-(2,3-dimethoxyphenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;6-(2-fluoro-3-methoxyphenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;6-(4-chloro-2-fluorophenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;6-[2-methoxy-5-(trifluoromethyl)phenyl]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;2′-methoxy-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2,3′-bipyridin-6(1H)-one;6-(3-chloro-2-methylphenyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;3′-chloro-2′-methoxy-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2,4′-bipyridin-6(1H)-one;6-[3-(morpholin-4-yl)phenyl]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;6-[3-(methylsulfonyl)phenyl]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;6-(1H-pyrazol-4-yl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;2′-methyl-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2,3′-bipyridin-6(1H)-one;6-[(3-methoxyphenyl)amino]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;6-anilino-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;6-[(trans-4-aminocyclohexyl)amino]-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2(1H)-one;N-(trans-4-{[6-oxo-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,6-dihydropyridin-2-yl]amino}cyclohexyl)cyclopropanesulfonamide;N-(trans-4-{[6-oxo-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,6-dihydropyridin-2-yl]amino}cyclohexyl)cyclopropanecarboxamide;1-(4-fluorobenzyl)-N-(trans-4-{[6-oxo-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,6-dihydropyridin-2-yl]amino}cyclohexyl)azetidine-3-carboxamide;2-(4-methylphenyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-(3-methylphenyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;2-(2,3-dimethylphenyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one;or2-{[3-(3-aminopropoxy)benzyl]amino}-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4(3H)-one.29. A pharmaceutical composition comprising a compound orpharmaceutically acceptable salt of claim 1 and pharmaceuticallyacceptable excipient.
 30. A method of treating cancer in a mammalcomprising administering thereto a therapeutically acceptable amount ofa compound or pharmaceutically acceptable salt of claim
 1. 31. A methodfor decreasing tumor volume in a mammal comprising administering theretoa therapeutically acceptable amount of a compound or pharmaceuticallyacceptable salt of claim 1.